Tag Archive for: jack aiello

Meet Jack Aiello: Myeloma Survivor and PEN Board Member

In this podcast, Jack Aiello, myeloma survivor and Patient Empowerment Network (PEN) board member, shares his myeloma story. Having been diagnosed with myeloma more than 20 years ago, Jack share his perspective as an advocate and his optimism about the future of myeloma care.

About the Guest:
Jack Aiello is a multiple myeloma survivor and patient advocate. Jack is involved with a number of advocacy organizations around the country, including serving on the Board of Directors for the Patient Empowerment Network. Learn more about Jack here: https://powerfulpatients.org/2019/01/03/jack-aiello.

Myeloma Highlights – #ASH16

MYELOMA HIGHLIGHTS FROM ASH CONFERENCE SAN DIEGO 12/2-6/2016

According to Jack Aiello (definitely not medically trained)

PREFACE

ASH 2016 Conference

ASH 2016 Conference

This is my 11th year attending ASH (American Society of Hematology) Conference, where 25,000 attendees from all over the world (hematologists/oncologists, lab researchers, oncology nurses, scientists & 300 pharma companies) present the latest research results via both oral presentations (1000) as well as posters (3000) on all blood cancers. This year there were nearly 700 abstracts (>100 clinical) on Myeloma alone, many of which were selected for oral presentation. I’m grateful to the IMF (www.myeloma.org) and their pharma donors for sending me to ASH so that I can learn and share my patient perspective with you.

Rather than attending talks on Biology, I typically focus on the Clinical Trials, which I’m able to understand and are more relevant near-term to patients. Even at that, there are overlapping MM oral sessions as well as 4’x6’ posters without reprints, so it’s always possible that I have not included something of interest to you or made a typo because I can’t read my own writing as detailed powerpoint slides are presented quickly. You might want to view the published abstracts at www.hematology.org and various press releases. [Wherever possible, I’ve listed Day-Abstract#-Lead Investigator after the trial results, e.g. {Mon-675-T. Zimmerman} and clicking on the abstract number will take you to the actual abstract.]

There are other ways to learn more about results from this conference. There are scheduled webinars (MMRF 1/11/17, IMF 1/12/17) which you can listen to live or by replay. You’ll also find some patient blogs (including mine) as well as MM expert video interviews posted on the IMF website (http://ash2016blogs.myeloma.org), Patient Power (www.patientpower.info), and Myeloma Crowd (www.myelomacrowd.org) among others. And all of us in the SF Bay Area should attend the LLS Blood Cancer Conference (which includes updates from ASH) Feb 4, 2017 (Register Now). Dr. Jeff Wolf of UCSF will do a great job presenting the latest information.

Presentations and posters of clinical trial results follow the same format: Background (including hypothesis), Study Objective, Design & Treatment schema, Patient Characteristics & Cohorts, Responses (include high-risk cytogenetics), Toxicity (hematological and non-hematological), Conclusion, and Next Step. Remember, the goal of Phase I (typically handful of patients) is to determine “Maximum Tolerated Dose”; Phase I/II and II (typically 25-75 pts) continues to measure dosage escalation and safety while looking at responses; and finally Phase III (several hundred patients) compares response rates between new and current treatments.

Treatment schedules are defined for stages of Induction, and optionally Transplant, Consolidation, and Maintenance with specified Randomization along the way; dosage amounts and scheduling are provided for each drug along with optimum number of treatment cycles (typically 28 days). Risk stratification correlates various techniques such cytogentics-FISH analysis (e.g. chromosome deletions and translocations) and gene-expression profiling (GEP).

HIGHLIGHTS (e.g. My Takeaways)

1. In Nov 2015, 3 new drugs were approved for Myeloma…Daratumumab, Elotumumab (both mAb’s) and Ixazomib (oral PI). At this ASH, trials were presented that provided results for using these drugs beyond their current FDA-approved indications such as Dara in combinations and Ixa before and after transplant.

2. Speaking of transplants (SCT), there were lots of abstracts on specific SCT usage…some contradictory. For example, one trial showed SCT plus consolidation benefitting MM pts while another trial showed no difference whether being treated with a single SCT, SCT + consolidation, or a tandem SCT.

3. There were 3 new drugs of interest: Nelfinivar, Selinexar and Venetoclax. Most impressive is that they were particularly effective in certain scenarios: Nelfinivar (with Velcade) for Vel-refractory pts; Selinexar alone for t(11;14) pts; and Ventoclax + dex for quad- and penta-refractory pts. Quad means refractory to Rev, Vel, Pom and Cfz, while Penta include Dara.

4. Minimum Residual Disease (MRD) testing is still not ready for prime time, but one doctor googled “Myeloma + MRD” and found 45 abstracts. MRD tests are certainly being added and reported in trials and while there’s good correlation between PFS/OS and MRD, it’s still not being used to determine subsequent treatment. Since MRD has the potential to guide therapy, stop therapy and change therapy, it’s something we patients need to keep on our radar.

5. There were several presentations on Immunotherapies (mAb’s, CAR-T’s and checkpoint inhibitors). However other than mAb’s like Dara, Elo, and Isatuximab (not yet approved), CAR-T and checkpoint inhibitors are still in a very early stage of evaluation.

6. More on checkpoint inhibitors. Dr Don Benson (OSU) explained that MM suppresses the immune system from doing its job. Inhibitors of the KIR ligand and PD1/PDL1 pathways enable NK cells and T-cells respectively to do a better job of finding and destroying MM cells. The concern, however, is that normal cells also have these built in checkpoints and you wouldn’t want the immune system destroying these cells as well. One doctor even mentioned that these are still “scary”.

COMMENTS AND DISCUSSIONS I FOUND PROVOCATIVE

7. “For patients in a CR, half will be MRD- and half will be MRD+.” B. Durie (IMF)

8. “I always see SMM patients again 1 month after diagnosis. It’s more important to know the tempo of their disease than risk factors.” S. Lonial (Emory)

9. “I’m afraid that some might interpret MRD- as a cure, which is not true.” J. Mikhael (Mayo)

10. “Half of SMM patients have MGUS-like disease and half are more like MM. If we only knew which patients were which, we would know who to treat.” S. V. Rajkumar (Mayo)

11. “It’s becoming more difficult to select the best treatment option for R/R MM patients.” P. Moreau (France)

12. When discussing the management of ND HRMM pts, Dr A. Dispenzieri (Mayo) reminded attendees that “high risk” not only includes chromosome abnormalities but also fitness/frailty assessment and access/cost of treatment. Whether TE or nTE, these patients should consider Velcade-based induction and maintenance. TE pts should consider Tandem SCT. And for renal-impaired, Velcade triplet is more effective than a Velcade-doublet.

13. “Although CR and MRD- should be the goal, not all patients get there and this needs to be considered.” N. Raje (UMass)

14. “For relapsed patients, doctors must consider previous treatments and responses. R/R MM pts should consider including POM.” N. Raje (UMass)

15. “Every 5 years, folks ask if SCT is dead. But it isn’t…not yet”. P. McCarthy (Roswell-NY)

16. “Today we are curing a subset of patients. We just don’t know who they are.” S. Lonial (Emory)

SMOLDERING MM

17. n=270 in 2 trials demonstrated that multiparameter flow cytometry may represent a better way (actually a “biomarker”) to classify HR SMM. Specifically this test classified these patients as MGUS-like (17%), Intermediate between MGUS & MM (66%) and MM-like (18%). Then 2-yr median Time-to-Progression (TTP) to MM/risk % was shown to be “not reached”/4%, 57 mos/25%, and 16 mos/58% respectively. {Sun-373-B. Paiva}

18. n=34 Elo (weekly)-Rev-dex in High Risk SMM, where HR is based on cytogenetics t(4:14), t(14:16, 17p- or +1q amplification. ORR was 82% (including CR 9%) and thus far no pts have progressed to active MM during or after protocol therapy. {Mon-976-I. Ghobrial}

FRONTLINE THERAPY FOR TRANSPLANT INELIGIBLE (NTE) PATIENTS

19. Ph 3, n=1600 NDMM pts, final PFS & OS results of the FIRST trial were presented comparing Rd continuous vs Rd 18 mos vs MPT. 4-yr PFS % (33 vs 14 vs 14) and median OS mos (59 vs 62 vs 49) and other factors showed overall benefit for continuous Rd. {Sat-241-T. Facon }

TRANSPLANTS

20. Ph 3, n=1400 NDMM pts, EMN02/HO95 MM trial VCD (R1) VMP or SCT (R2) VRD consolidation or none followed by Rev maintenance till progression, examined the impact of consolidation, which benefitted std but not HR pts. Best news was that 3yr OS from R2 was 86% and 87% respectively.{Sat-242-P. Sonneveld}

21. Additional analysis was provided from the EMN02/HO95 MM trial shown above. Specifically, the SCT arm did show benefit over the VMP arm for all pts, e.g. ORR 86% vs 75% and 3yr PFS 65% vs 57%; for HR pts 3yr PFS was 52% vs 30%. So ultimately HR MM pts benefitted by SCT but not from consolidation (above). {Mon-673-M. Cavo}

22. Ph 3, n=581 Myeloma XI study investigated a response-adapted approach to induction. Specifically if pts achieved less than VGPR to induction (IMID regimen), they would be randomized to be given an additional regimen (PI based) before SCT. The consolidation side improved median PFS from 20 to 30 mos. For those having a transplant, the PFS was even better (31 mos versus 55 mos). However even Transplant Ineligible pts showed PFS benefit with consolidation of 14 vs 20 mos. {Sat-244-G. Jackson}

23. n=42, Ph 2. IxaRd –> SCT -> IxaRd -> Ixa maintenance for NDMM pts. Note this all-oral therapy (except for SCT). VGPR (CR) or better at the end of Induction, SCT and Consolidation were 36% (12%), 78% (38%), and 77% (44%) respectively. Adverse events were well-tolerated with no grade 3/4 neuropathy. If the future Dara may be added to this regimen. {Mon-674-P. Moreau}

24. n=76, Ph 2. KRdx4 -> SCT -> KRdx4 -> KRd maintenance (x10) -> Rev maintenance. Analysis were done after cycles 4, 8, and 18. At C18, ORR was 94% with a very high 86% in CR. [BTW, with no SCT for another group of 53 pts, C18 ORR/CR was 90%/40%.] MRD was done by both Flow and NGS. At C8 and C18 MRD- was 86%/64% and 97%/71% respectively by each method. For HRMM pts, ORR was 96% (81% CR) and C18 MRD- was 90%/63%. And 3yr PFS/OS was 86%/95%. When asked to compare this KRd regimen with the IxaRd regimen results above, the speaker said KRd speeds up response but has higher toxicity. {Mon-675-T. Zimmerman}

25. n = 46, KRdx4 -> SCT -> KRdx4 -> Rev maintenance (nearly the same as above) resulted in similar outcomes sCR = 57%, >= VGPR = 91%, MRD- = 70% with no neuropathy. {Mon-1142-G. Jackson}

26. n=111, Ph 2. KTdx4 -> SCT –> KTd x4 (T lowered from 200mg to 50mg). ORR after consolidation was 95% (CR=64%). Overall 3yr PFS and OS were 68% and 90% respectively. For HR pts, responses and OS were about the same while PFS was less. {Mon-1141-R. Wester}

27. n=750 pts were randomized into 3 arms. Arm 1, denote ACM, received one auto SCT, 4 cycles of RVD consolidation, then Rev maintenance until progression. Arm 2, denoted TAM, received a tandem (two) SCT’s and Rev maintenance until progression. Finally Arm 3, denoted AM, received a single auto SCT, then Rev maintenance until progression. After 38 months, the PFS (57%/56%/52%) and OS (86%/82%/63%) were comparable in all three groups. Furthermore, when looking at subgroups such as High Risk, there was no differences (all about 24% PFS and 75% OS). Even overall secondary primary cancers (SPMs) were all about 5%. {Tue-LBA-1-E. Stadtmauer}

TREATMENTS FOR RELAPSED/REFRACTORY (R/R) PATIENTS

28. MRD results were presented for the recent POLLUX (DaraRd vs Rd) and CASTOR (DaraVd vs Vd) trials, which resulted in FDA approval of using Dara with Rev or Vel. MRD- outcomes were typically about 3x in the Dara arms versus the non-Dara arms. Further, MRD- for Dara-Rd was about 2x compared with the Dara-Vd arm (25% vs 10% evaluated by NGS with 10-5 sensitivity). {Sat-246-H. Avet-loiseau}

29. Another update of the Pollux study (DRd vs Rd) for RRMM pts showed benefits in ORR (94% vs 77%), 18 mos PFS (77% vs 50%), and MRD- (25% vs 6%). ORR for HRMM was 89% vs 67%. {Sun-489-P. Moreau}

30. n=41 RRMM pts on Dara-Pom-dex trial also examined “retreatment” with Dara. ORR 89% for Dara & Pom naïve but nearly 35% ORR for pts refractory to both Dara and Pom {Sun-492-A. Nooka}

TARGETED THERAPY

31. Ph 3, n-432. Tourmaline-MM1 study Ixa-Rd vx Rd for RR MM pts that resulted in Ixazomib approval Nov 2015. This sub-analysis examined patient expression level of c-MYC (proto-oncogene regulation cell proliferation & cell death. High c-MYC expression pts showed a 6 month PFS benefit on the Ixa-Rd over Rd. {Sat- 243-A. Di Bacco}

NEW DRUGS

32. n=34 Nelfinavir is an approved, generic oral drug, and HIV protease inhibitor used to treat AIDS. When combined with Vel-dex (NVd) for Vel-refractory ASH16pts (and 76% were also Rev-refractory), ORR = 65% include 5 pts achieving VGPR. {Sun-487-C. Driessen}

33. n=66 (inc 30 pts had t(11;14) MM. Ph 1. Venetoclax, BCL-2 inhibitor, single agent for RRMM showed 21% ORR but 40% ORR for t(11;14) pts (88% if also high BCL-2 expression). {Sun-488-S. Kumar}

34. n=65 Venetoclax + Vel-d for RRMM pts. Overall ORR 67% with best responses ORR=97% for Vel non-refractor and 1-3 prior tx lines. Worst ORR for >6 tx lines (20%) or Velcade-refractory (31%). Likely Ph 3 to be Ven-Vd vs Vd. Higher BCL-2 expression means better ORR. {Mon-975-P. Moreau}

35. n=45, Ph 2 Pembrolizumab (checkpoint inhibitor Keytruda) + Pom-dex for RRMM, all refractory to Rev, 73% double refractory. ORR 65% (inc 27% >= VGPR and median PFS 17 mos. However ASE’s included 40% grade 3 neutropenic and . pts required dose reduction. {Sun-490-A. Badros}

36. n=79 including 48 quad (Rev-Vel-Pom-Cfz) and 31 penta (quad + Dara) refractory. Selinexor (80 mg 2x/wk) (oral XPO1 inhibitor) and dex (20 mg 2x/wk) regimen (Sd) goes by the name STORM study. ORR was about 20% for both quad and penta but also had grade 3/4 hematological events. Median OS was 9.3 mos. {Sun-491-D. Vogl}

37. n=12, Phase 1 study of Selinexor-Cfz-d in RRMM pts. These 12 pts were also refractory to Cfz. ORR for this group was 67% (15% >= VGPR) with 3.7 mos PFS. {Mon-973-A. Jakubowiak}

38. n=22, Ph 1b/2 study of Selinexor (100 mg/wk)-Vel-d (SdB) for RR MM pts, including those refractory to Vel (STOMP trial). Overall ORR=77% (inc 9% CR, 18% VGPR). For Vel-refractory, ORR=67%, while Vel-exposed/naïve had 100% ORR. {Mon-977-N. Bahlis}

39. n=12, Pilot Study of CAR-T CD19 in conjunction with salvage (2nd) SCT for advanced MM. Method: 2 weeks after the SCT, 5 x 107 CAR-T cells are infused. Of these 12 pts, 3 pts had a VGPR and longer PFS than from their first SCT. One patient (featured on the cover of Parade Magazine several months ago) had a 16 mos PFS but then relapsed and is now in a 12-mos CR with Dara. Only one episode of cytokine release for these 12 pts. {Mon-974-A. Garfall}

OTHER RESULTS

40. n=113 For Light Chain MM patients who follow their disease with 24-hr urine analysis (UPEP), the Serum Free Light Chain test offered better correlation with clinical outcomes (e.g. PFS) than urine assessments….and is certainly easier on these patients. {Sun-376-T. Dejoie}

41. There were several presentations on racial disparities. These included {Mon-844-M. Fiala}and {Mon-846-A. Rosenberg}that examined the usage of SCT’s by African American MM pts. The first concluded that when elimininating health disparities and postential access barriers, black pts are will 37% less likely to utilize an SCT. The second focus was on California patients but came up with a similar number 30%. This poster {Sun-3544-S. Ailawadhi}examinedMM complications (CRAB symptoms) among different racial groups with blacks having the highest rate of complications, perhaps being due to reduced access to drugs/supplemental insurance coverage.

42. An interesting study for Myeloma Cast Nephropathy (kidney impairment) comparing Haemodialysis with High Cut-off vs Standard High Flux Dialyzer in pts receiving Velcade-based therapies. With Haemodialysis, 1/2 the pts became dialysis-free versus only 1/3 in the Standard control group. {Mon-978-JP Fermand}

43. n=41 This trial study the efficacy and side effects from administration of Daratumumab via sub-Q injection in R/R MM pts. For pts on the recommended dose of 1800mg given over 30 minutes, the ORR was 41% and Infusion Reaction Rates were lower than with Dara IV infusion. And when asked about pain or bruising at the infusion site, Dr Usmani said that neither were problems. This has the potential to reduce infusion times from six or eight hours to 30 minutes. {Mon-1149-S. Usmani}

SUMMARY

For someone diagnosed with stage III MM 22 years ago with only 2 treatment options available (MP or VAD-SCT) and given 2-3 years expected survival, I’ve seen incredible progress since 2003 when Velcade was first approved. While there continues to be unanswered questions, we now have many more effective treatments for MM, providing patients with better opportunities to manage their disease.

GLOSSARY (according to Jack) Drug (brand names) by Drug Class/Category

IMID – Immunomodulary Drug

T – Thalidomide

R – (Lenalidomide) Revlimid

Pom – Pomalidomide (Pomalyst)

PI – Proteasome Inhibitor

V- Velcade (Bortezomib)

Cfz – Carfilzomib (Kyprolis)

I, Ixa – Ixazomib (Ninlaro)

mAb – Monocloncal Antibody

D, Dara – Daratumumab (Darzalex)

E, Elo – Elotuzumab (Empliciti)

Isa – Isatuximab (SAR650984)

HDAC – histone deacetylase inhibitors

Pano – Panobinostat (Farydak)

Steroids

P – Prednisone

D or d – Dexamethasone

Chemotherapy Drugs

C – Cyclophosphamide (Cytoxan)

M – Melphalan

Treatment Measurements

EFS – Event-free Survival

ORR – Overall response (>=PR)

OS – Overall Survival

PD – Progressive Disease

PFS – Progression-free Survival

PFS2 – PFS + next-line treatment PFS

TTP – Time to Progression

TTR – Time to Respond

Treatment Response

CR – Complete Response: No sign of MM (0 M-spike)

nCR – Near CR (positive M-spike, may be same as VGPR)

MR – Marginal Response: 0-50% reduction in MM

PR- Partial Response: 50% reduction in MM

SD – Stable Disease i.e. no response but also not worse

sCR-Stringent CR: CR+ normal FLC & no clonal cells

VGPR – 90% reduction in MM

MRD – Minimum Residual Disease typically by Flow Cytometry (NGF) or DNA sequencing (NGS) to provide more accurate measure of MM.

Side Effects

AE (ASE) – Adverse Event (Adverse Side Effects)

DVT – Deep Vein Thrombosis (blood clots)

MTD – Maximum Tolerated Dose

ONJ – Osteonecrosis of the Jaw

PE – Pulmonary Embolism

PN – Peripheral Neuropathy

QOL – Quality Of Life

VTE – Venous Thromboembolism (PE + DVT)

Tests/When to treat?

CRAB – High Calcium, Renal, Anemia, and Bone…

CRABi – CRAB + “i” increased infections

FLC – Free Light Chain

SCT – Auto stem cell transplant.

TE, NTE – Transplant Eligible of Not TE

“d” and “D” – Typically both mean Low-dose Dex (40 mg/week) these days

MGUS – Monoclonal Gammopathy of Undetermined Significance

SMM – Smoldering MM

Pt(s) – Patient(s)

n – Number of pts

R/R- Relapsed/Refractory, Ref defined progressing while on Tx or within 60 days.

HR – High Risk

Day 2: Can anything compare with eliminating 24-hr urine collections?

Editor’s note: This blog was originally published by Jack Aiello on the International Myeloma Foundation’s website.


ASH 2016Today’s events began with 9:30 a.m. education program on 1) managing Newly Diagnosed High-Risk (HR) Multiple Myeloma patients 2) Sequencing treatments, and 3) the role of stem cell transplant (SCT) and maintenance. Dr Angela Dispenzieri spoke on the first topic, and she reminded the audience that “High-Risk” doesn’t just mean cytogenetic factors like del(17p), but also patient frailty or a patient’s access to and the cost of drugs must be considered. She also reminded folks that the ISS staging using albumin and beta 2 was revised, denoted as R-ISS, to include serum lactate dehydrogenase (LDH) and cytogenetic HR factors that make up much of stage 3. Now, multiple myeloma patients in stage 1 = 28%, 2 = 62% and 3 = 10%. And prognostic 5 year OS rates for stages 1-3 are 81%, 60%, and 40%, respectively, which explains why there’s a significant effort to determine better treatments for stage 3 patients. Evidence shows that HR patient should be treated with Velcade®-based regimens at induction, consolidation, and maintenance.

Dr. Noopur Raje (SF Support Group folks will know her because she spoke at our past Oct ’16 support group meeting) tackled the second topic. She stated that treatment goals should always be to obtain good and deep responses while maintaining/improving quality of life. Should MRD- be a goal? Yes, because it translates into better progression free survival (PFS) and overall survival (OS). However, she said, “Not all patients will obtain a Complete Response (CR) and MRD-, and this needs to be considered.” Relapsed/refractory MM patients need to assess past treatments and responses before selecting future treatments. Should everyone get an MRD test? The panel of experts suggested that this isn’t ready for “prime-time” yet, but rather should be done within a clinical trial.

Finally, Dr. Philip McCarthy spoke about transplants, beginning with “Every 5 years folks ask if the SCT is dead. But it isn’t…not yet.” He proceeded to show many trial results displaying PFS and OS benefits with transplant as well as maintenance.

Next, I attended some oral presentations that provide some provocative information: 1) Using flow cytometry may represent a better way to classify HR SMM (Abstract #373); 2). Next generation sequencing can produce more accurate results than FISH when classifying HR MM patients (Abstract #374); 3) For those with Light Chain Myeloma, the serum free light chain tests offer improved sensitivity and better correlation with clinical outcomes than does the 24 HR urine assessment (Abstract #376). That last one provides the patient both benefit and ease of FLC test instead of a urine collection…a real winner.

In the middle of the afternoon, I had a great meeting with folks at Sanofi.  If you’ve had a transplant, you may well have used the Sanofi drug called Mobilzil which mobilizes your stem cells from your marrow into your blood stream for harvest. But I also picked up a flyer that shows Sanofi beginning a randomized phase 3 trial with Isatuximab (CD38 mAb) +/- Pom & dex for RR MM patients.  All the drug costs are being covered by Sanofi so in addition to being closely monitored by your oncologist, there’s no drug costs. In the Bay Area, we’re quite familiar with Isatuximab because UCSF has conducted several earlier trials with this drug, previously known as SAR650984. Down the road it will be interesting to see how this drug compares with the other CD38 mAb Darzalex® (Daratumumab).

The afternoon ended with more oral presentations, this time on new therapies: 1) Nelfinavir is an old, generic oral drug that the FDA approved as an HIV protease inhibitor. A group in Switzerland has shown that when combined with Velcade and dex (NVd) and given to Velcade-refractory patients, ORR was 65% (Abstract #487); 2) Venetoclax (BCL-2 inhibitor) has single agent activity for MM patient but in particular has an ORR of 40% in patients with t(11:14) (Abstract #488); 3) Selinexor (XPO1 inhibitor) plus low-dose dex (Sd) shows about a 20% ORR for patients refractory to Rev, Velcade, Pom, and Cfz (“quad-refractory”) and even Dara (“penta-refractory”) (Abstract #491). The exciting thing about all 3 of these drugs is that they represent different mechanisms of action than we have in today’s therapy arsenal.  However, it’s important to note that these were all small trials (20-70 pts) and all drugs had some significant, but hopefully manageable, side effects. Finally, Pembrolizomib (checkpoint inhibitor) with Pom-dex for RR MM pts showed ORR in 65% of patients, but it too, also had side effects that required half the patients to dose-reduce (Abstract #490).

Finally, poster #3558 caught my attention “Real-World Trends in Treatment Use, Healthcare Costs, and Overall Survival Among Patients with Multiple Myeloma.” One of the conclusions states that total healthcare costs have risen steadily since 2000. However, drug costs increased slower than other cost components and remained a minority of the costs.

On that note, it’s been a long day and tomorrow’s first oral presentation is at 7 a.m.

Myeloma Highlights from #ASH15

According to Jack Aiello (definitely not medically trained)

PREFACE

This is my 10th year attending ASH (American Society of Hematology), where 25,000 attendees from all over the world (hematologists/oncologists, lab researchers, oncology nurses, scientists & 300 pharma companies) present the latest research results via both oral presentations (1,000) as well as posters (3,000) on all blood cancers. This year there were nearly 800 abstracts (>100 clinical) on Myeloma alone, many of which were selected for oral presentation. I’m grateful to the IMF (www.myeloma.org) and their pharma donors for sending me to ASH so that I can learn and share my patient perspective with you.

Rather than attending talks on Biology, I typically focus on the Clinical Trials, which I’m able to understand and are more relevant near-term to patients. Even at that, there are overlapping MM oral sessions as well as 4’x6’ posters without reprints, so it’s always possible that I have not included something of interest to you or made a typo because I can’t read my own writing as detailed powerpoint slides are presented quickly. You might want to view the published abstracts at www.hematology.org and various press releases. [Wherever possible, I’ve listed Day-Abstract#-Lead Investigator after the trial results, e.g. {Sat-25-B. Durie} and clicking on the abstract number will take you to the actual abstract.]

There are other ways to learn more about results from this conference. There are scheduled webinars (IMF 1/7/15, MMRF 1/13/15) which you can listen to live or by replay. You’ll also find some patient blogs (including mine) as well as MM expert video interviews posted on the IMF website (www.myelomal.org) and Patient Power (www.patientpower.info) among others. And all of us in the SF Bay Area should attend the LLS Blood Cancer Conference (which includes updates from ASH) Jan 23, 2016 (Register Now). Dr. Jeff Wolf of UCSF will do a great job presenting the latest information.

Presentations and posters of clinical trial results follow the same format: Background (including hypothesis), Study Objective, Design & Treatment schema, Patient Characteristics & Cohorts, Responses (include high-risk cytogenetics), Toxicity (hematological and non-hematological), Conclusion, and Next Step. Remember, the goal of Phase I (typically handful of patients) is to determine “Maximum Tolerated Dose”; Phase I/II and II (typically 25-75 pts) continues to measure dosage escalation and safety while looking at responses; and finally Phase III (several hundred patients) compares response rates between new and current treatments.

Treatment schedules are defined for stages of Induction, and optionally Transplant, Consolidation, and Maintenance with specified Randomization along the way; dosage amounts and scheduling are provided for each drug along with optimum number of treatment cycles (typically 28 days). Risk stratification correlates various techniques such cytogentics-FISH analysis (e.g. chromosome deletions and translocations) and gene-expression profiling (GEP).

 

HIGHLIGHTS (e.g. My Takeaways)

  • In the large French/US study comparing early versus late SCT, the French showed a PFS benefit but not three-yr OS benefit (both arms about 83%), maybe because trial results are not mature. However, the French part of the study only uses one year of maintenance, whereas the US uses maintenance until progression.  The US has yet to report data so will maintenance make a difference to the outcome?  We’ll see.
  • For relapsed patients, treatment isn’t as clear cut but with the recent approvals of Darzalex (Daratumumab), Ninlaro (Ixazomib), and Empliciti (Elotuzumab), patients have more options as they combine each of these with the baseline Rev-dex. How clinicians will use or “sequence” Dara-Rd, Ixa-Rd, and Elo-Rd will likely be better understood over the next one to two years, making it even more beneficial for patients to have a Myeloma expert as part of their treatment team.
  • The Ultra High Risk (plasma% > 60%, FLC ratio > 100, >1 focal lesions) Smoldering multiple myeloma patients (SMM) have already been re-classified as MM pts, even without CRAB criteria. Other SMM pts that have some indication of high-risk features (e.g. perhaps plasma% > 10% and one of FLC ratio > 8 or cytogenetics such as del17p) should investigate participation in a clinical trial such as E3A06 to determine the efficacy of early treatment.
  • Three-drug VRd therapy for newly diagnosed patients has been shown to have longer progression free survival (PFS) and overall survival (OS) than two drugs and should be considered the standard of care. Mayo’s M-SMART (msmart.org) treatment protocol recommendation for newly diagnosed standard and intermediate risk patients has been updated from Rd to VRd (still KRd for high-risk).
  • Minimum Residual Disease (MRD) testing is not ready for prime time, but it has good prognostic value for MM patients, similar to CR being a good prognostic indicator. MRD still needs to be consistently defined using NGS or Flow (8-color/2 tubes). Trade-offs include NGS needs diagnostic sample and has higher cost while Flow needs “fresh” samples. And more trials need to integrate MRD so that clinicians can eventually use MRD results to help guide future treatment plans.  And probably, MRD needs to be combined with PET-CT to get the complete picture.
  • You’ll see reports below that look at survival outcomes such as Progression Free Survival (PFS) and Overall Survival (OS). However, with new treatments available, OS (i.e. death) become less meaningful for a particular drug. Perhaps the assessment of targeted biomarkers will become better measurements of drug efficacy.

 

COMMENTS AND DISCUSSIONS I FOUND PROVOCATIVE

  • We are still trying to determine the role of maintenance. There have been or are currently 242 clinical trials involving maintenance (including “consolidation and “continuous therapy”). Even vaccines (e.g. dendritic cells) are being tested as maintenance. T. Facon (France)
  • Re Using Emerging Therapies up front: “Adding later does not add up.” S. Kumar (Mayo)
  • Re Early Treatment: “In most cancers (lung, breast), early diagnosis and treatment is a prerequisite to OS improvement. When we wait, clones have a chance to develop more aggressive subclones. But we must work to develop predictive biomarkers.” J. San-Miguel (Spain). However, “Should you over-treat 30% of HRSMM pts at the risk of under-treating 70%? What about toxicity? You need more evidence-based medicine.” P. Moreau (France)
  • Flow (NGF) & NGS measure myeloma inside the bone marrow while PET-CT measures myeloma outside the bone marrow. A. Orfao (Spain)
  • I attended an FDA presentation where each FDA MD reviewed their criteria for approving Ixazomib, Daratumumab, and Elotuzumab respectively, citing the specific trial as well as primary and secondary endpoint results. Then Drs. S. V. Rajkumar (Mayo) and P. Richardson (Dana Farber) discussed using these new drugs as front-line and relapsed therapies respectively. Dr. Rajkumar began “Myeloma treatment is moving so fast, the Education Session I gave 2 days ago is already out of date.” To use these drugs front-line, they would be need to be “off-label” and it’s better to use them within a clinical trial for newly diagnosed pts. Dr. Richardson explained the Rd is the “backbone” and we can add V, K, I, D, and E (and SAR in the future?). We’ll understand more about sequencing these combinations in the next 1-2 yrs.

    Convention Hall

    Convention Hall

 

SMOLDERING MM

  • “If it’s smoldering, is there a fire?” S. Lonial (Emory) and “Some pts with SMM really have MGUS and others MM…we just don’t know which ones.” S. V. Rajkumar (Mayo)

 

FRONTLINE THERAPY FOR TRANSPLANT ELIGIBLE PATIENTS

  • Ph 1/2, n=48 NDMM pts, including 30% HR, Panobinostat (10mg) + RVd. ORR after 4 cycles was 94% (CR/nCR 46%…compared with past trials RVd-only CR is 10-20%) and 14 of 26 pts were MRD- before their SCT. ASE Grade 3 nausea 6% and PN 4%. {Sun-187-J. Shah}
  • Ph 3, n=525 NDMM pts, VRd vs Rd. Overall Response Rate ORR (82% versus 72%), CR (16% versus 8%) Progression Free Survival PFS (43 versus 30 mos) and Median Overall Survival OS (75 versus 64 mos) all showed the benefits of triplet therapy over doublet. {Sat-25-B. Durie}
  • Ph 3, n>2000 NDMM pts comparing KCRd with CRd (and CTd). It showed the 4-drug regimen that added Carfilzomib resulted in higher >= VGPR (82% vs 62% vs 55%) and that KCRd had lower (!) hematological suppression than CRd (9% vs 16%). {Sun-189-C Pawlyn, UK}

 

FRONTLINE THERAPY FOR TRANSPLANT INELIGIBLE PATIENTS

  • {FIRST subgroup analysis} n=142 High Risk [del 17p, t(4;14) or t14;16)] NDMM pts randomized to 3 arms: Rd till progression vs Rd 18 cycles vs MPT 12 cycles. In non HR pts, median PFS was 31 mos vs 21 mos vs 25 mos while HR pts were 8/18/15 mos. In non HR, 3yr OS % was 77% vs 71% vs 65% while HR pts were 41/40/47%. So while Rd till progression was the winner overall in the FIRST trial, it did not do so well comparably in High-Risk pts. {Mon-730-H. Avet-Loiseau}
  • Ph 2, n=70 NDMM pts, Ixazomib-Cytoxin-Dex (ICd) randomized to C = 300 or 400 mg all oral therapy. Plus Ixa maintenance. Early ORR results better in C=300 arm (78% vs 75%) and >=VGPR (28% vs 21%). PFS @ 9 mos was 90% but data not yet mature. {Sat-26-M. Dimopoulus}
  • Ph 2, n=40 NDMM pts, “RVd-lite” study Rev = 15mg, days 1-21; Vel = 1.3 mg/m2 once/week; dex = 40 mg/wk for pts <75yo and 20 mg /wk otherwise. After 4 cycles, ORR was 90% (including CR 25%), 2 yr PFS is 68%. {Mon poster-4217-E. O’Donnell}

 

TRANSPLANTS

  • Ph 3, n=389 NDMM pts, SCT vs Cytoxin-Rd followed by RP vs P maintenance. SCT showed improvement in median PFS (43 vs 29 mos) and 4-yr OS (86% vs 73%) Median PFS from the start of maintenance was 38 mos for RP vs 29 mos for R-only but 3-yr OS was similar (83% vs 88%). Of note, at the start of maintenance, MRD- was 48% for the SCT arm vs 28% for CRd, even though CR and VGPR numbers were very close. {Sun-392-F. Gay, Italy}
  • Ph 3, n=700 70 NDMM pts, “Determination” RVd +/- SCT + RVd consolidation + R maintenance. The French side of this study showed benefits in the SCT arm for ORR (88% vs 78%), CR (59% vs 49%), 4-yr PFS (47% vs 35%), and MRD- (80% vs 65%) but no OS difference (83%), which could be due to the short timeframe as well as early crossover to the SCT arm. {Sun-391-M. Attal}
  • Ph 3, n=174 (of 297 enrolled) prior SCT pts. Salvage SCT was defined as a 2nd SCT after relapse > 18 mos from prior SCT. All pts were re-induced with Velcade-Doxorubicin-Dex (PAD) and randomized to either 2nd SCT vs 12 wks Cytoxin with crossover. ORR to re-induction was 79%. 4yr OS was 69% (2nd SCT) vs 61% (crossed over to 2nd SCT) vs 50% (no 2nd SCT), so beneficial to have salvage SCT sooner. {Sun-394-G. Cook, UK}

 

TREATMENTS FOR RELAPSED/REFRACTORY (R/R) PATIENTS

  • {ASPIRE subgroup Analysis} Ph 3, n=100 HR RRMM pts. KRd vs Rd, where High Risk is one of del 17p (>60% of plasma cells), t(4;14) or t(14;16). Median PFS for HR was 23 mos vs 14 mos (compared with std risk 30 mos vs 20 mos). ORR from HR was 79% vs 60% (compared with std risk 91% vs 74%). {Mon-731-H. Avet-Loiseau}
  • {Endeavor subgroup analysis}Ph 3, n=465 RRMM , Kd vs Vd outcomes for 1 and 2+ prior lines of therapy. Median PFS: 1 line 22 vs 10 mos; 2+ lines 15 vs 8 mos. ORR: 1 line 82% vs 66%; 2+ lines 72% vs 60%. This presentation concluded that Kd should be considered in pts who have progressed on Rev maintenance. {Mon-729-P. Moreau}
  • {Eloquent-2} Ph 3, n=646 RRMM pts, Elotuzumab +/- Rd. Elo-Rd showed PFS benefit 4.5 mos (19.4 vs 14.9) with very similar Adverse Events except infusion reaction in 10% pts (of which 63% were in the first infusion). {Sat-28-P. Richardson}
  • Ph 1b, n=98 RRMM pts with at least 2 lines of prior therapy. Dara + Pom-d. 67% of pts refractory for both IMI and PI but Pom-naïve. ORR 71% (nearly same for double-refractory) including 9% CR. PFS @ 6 mos is 66%. ASE’s similar to Pom-d alone other than half of pts had IRR (Infusion Rate Reaction) during the first infusion but only 3% at 2nd {Mon-508-A. Chari}
  • Combination of two Ph 2 trials, n=148 pts, double-refractory to a PI & IMID. Daratumumab alone (!). Dosage 16mg/kg. ORR= 31%; median PFS was 7.4 mos; 1 yr OS 69%. For pts who responded, the OS results were even better: OS for MR/SD pts = 17.5 mos, and not reached for >=PR. 10-18% of pts experienced some hematological ASE’s. {Sat-29-S. Usmani}
  • Ph 2, n=32 RRMM pts. Daratumumab (16mg/kg) + Rd. ORR 81% (compared with Rd ORR 61-66% for similar pts); 63% >= VGPR. PFS @ 12 mos 91% (compared with Rd median PFS 11-15 mos for similar pts) and PFS@18 mos 72%. OS@18 mos 90%. ASE’s similar to Rd-alone other than some infusion reaction, usually only with the first infusion. {Mon-507-T. Plesner, Denmark} Note: Dr. Torben Plesner was the first doctor to treat an MM pt with Dara in 2007.
  • Ph 2, n=152 RRMM pts, 50% prior Velcade treatment, 1-3 prior therapies. Elotuzumab (10 mg/kg) +/- Vd. Benefits in >= VGPR (36% vs 27%), median PFS (10 mos vs 7 mos) while ORR about the same (65% vs 63%). Grade 3/4 AE higher in EVd (71%) than Vd (60%), most of this difference being infections (23% vs 15%). {Mon-510-A. Palumbo}
  • {Endeavor subgroup analysis}Ph 3, n=210 RRMM high-risk pts, Kd vs Vd. PFS benefit ~3 mos (8.8 vs 6 mos); ORR 72% vs 58% (CR 16% vs 4%). 1-2% (3% vs 1%) experience more cardiac issues in the Kd arm. {Sat-30-S. Usmani}
  • {Tourmaline-MM1} Ph 3, n=722 RRMM pts, Ixazomib (4mg days 1, 6, 15) +/- Rd (IRd vs Rd). Note that 70% pts previously had Velcade but were not refractory to Rev or PI. Benefits seen in ORR (78% vs 72%, including CR 12% vs 7% and VGPR 36% vs 32%) and Median PFS (20.6 vs 14.7 mos, including del17 21 mos vs 10 mos). OS data not presented due to lack of maturity. {Mon-727-P. Moreau}
  • A pooled analysis of 3 trials example the usage of Pom-dex in 355 pts with moderate kidney involvement (versus 713 pts with no renal impairment. Similar ORR (30% vs 34%), median PFS (4 mos vs 5 mos) and median OS (11 mos vs 14 mos) as well as Grade 3/4 AEs. {Sun poster-3031-D. Siegel}

 

MAINTENANCE (including CONSOLIDATION)

  • Ph 3, n=1964 pooled analysis examined CR patients who received maintenance or not, and determined a significant 5-yr OS benefit (80% vs 54%) and 5-yr PFS benefit (52% vs 19%) for pts on maintenance. {Sat poster-1974-C. Cerrato}

 

NEW DRUGS

  • Ph 2, n=68 RRMM pts. Carfilzomib +/- Filanesib (ARRY-520), a kinesin spindle protein (KSP) inhibitor. Adding FIL show some benefit: ORR 28% vs 24% and median PFS 9 mos vs 4 mos. {Mon-728-J. Zonder}
  • {Keynote-023} Ph 1, n=17 R/R pts, including 50% refractory to Rev. Pembrolizumab (anti PD-l Antibody) + Rd. Pembro dose confirmed at 200mg. ORR 76% (including 56% for pts Rev-refractory), with 4 of 17 pts VGPR (24%). {Mon-505-J.San Miguel}
  • Ph 2, n=27 RRMM pts, 36% HR, 90% Rev-refractory, 70% refractory to both IMID and PI. Pembrolizumab (anti PD-l Antibody) + Pom-d. ORR 60% (including 55% for double-refractory and 50% HR). Gr3 AEs 10-20% pneumonia/infection. {Mon-506-A. Badros}
  • Selinexor (KPT-330), which enhances the natural cell defenses against cancer, was combined with PI’s Velcade or Carfilzomib and shown to potentially overcome drug resistance {Sunday poster-3048-D. Sullivan}. And when combined with Cfz-dex in a Ph 1 trial for RRMM pts including those refractory to Cfz, >= PR was 75%, although results are still early. {Mon poster-4223-A. Jakubowiak}

ASH 2015

OTHER RESULTS

  • A presentation on Social Media for Hematologists was titled “So You Know How to Treat, But Do You Know How to Tweet?” and discussed the increased usage of Twitter during ASH15 from more than 5K participants, including a number of support group leaders (SGL) in attendance. For a summary of all the SGL tweets, use the hashtag #IMFASH15.
  • I attended a meeting conducted by Takeda on the usage of their new oral PI Ixazomib (Ninlaro). It’s indicated for pts who have had 1 prior treatment and used with Rev-d. It needs to be taken on an empty stomach (1 hr before or 2 hrs after a meal) in order to ensure efficacy. And while the standard dosage is a 4mg capsule, it also comes in 3 mg and 2.3 mg capsules. The name Ninlaro? While in development, the drug was called MLN9708. So Ninlaro comes from Nine (minus the “e”) plus “oral” spelled backwards.
  • I attended a session on Patient-Reported Outcomes (PRO’s) which examine Physical, Mental and Social Health in clinical trials and patient care. PRO data is used by Prescribers, Regulators, and Healthcare Payers. You can learn more about this at healthmeasures.net and www.nihpromis.org.
  • This study examined n=693 SCT pts who had various induction therapies RVd, Rd, Vd, and CVd, specifically at pre-SCT and post-SCT >= VGPR results. Pre-SCT responses were 57%/42%/51%/45% and post-SCT were 65%/63%/65%/58%, all quite close. However, maintenance treatment improved 3-yr PFS to 55% vs 39% for no maintenance. In conclusion, when having an SCT, the choice of induction treatment is less important than maintenance {Sun-396-R. Cornell}
  • MRD was evaluated in the French side of the IFM/DCFI 2009 “Determination” trial. Of n=700 pts, 178 pts were evaluated by NGS after maintenance. For CR pts, 83% were MRD- but 17% were MRD+. {Sat-191-H. Avet-Loiseau}
  • CAR-T therapy for myeloma treatment resulted in several oral presentations. In pre-clinical models, SLAMF7-CAR-T cell therapy was shown to be safe and effective in MM treatment. {Sat-115-S. Danhof}. And a company called Cellectis in France showed that they can use healthy donor T-cells and engineer them for a double KO (both TRAC and SLAMF7) to enhance antitumor activity. {Sat-116-R. Galetto}. And a “Late-Breaking Abstract” highlighted a Ph 1 study of 12 RRMM pts using CAR-T cells engineered as anti-BCMA CARs (CAR-BCMA). The B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells in 60-70% of MM pts. To participate in this NCI trial, pts must have had 3 lines of prior therapy and BCMA expression. Pts were given 3 days of Cytoxin and fludarabine beforehand, but no transplant. All 12 pts achieved at least stable disease (SD) with 1 sCR, 1 VGPR, and 2PR’s, typically better results as dosages increased. Pts incurred substantial toxicity (fever, kidney, cytokine release, and more but these AE’s were all reversible. Still, a follow-up trial eligibility criteria will include pts have less that 50% plasma cells. {Tue-LBA-1-J. Kochenderfer}
  • MRI & PET-CT were evaluated in the French side of the IFM/DCFI 2009 “Determination” trial. At diagnosis for n=134 pts, MRI and PET-CT were positive for 95% and 91% of pts. After 3 cycles of RVd, MRI was still positive in 93% but PET-CT in only 55% and was a better prognostic indicator for PFS but not OS. Before maintenance, MRI was not a good prognostic indicator for PFS or OS but PET-CT results were associated with significant improvement in both PFS and OS. As such, an MRI may not be needed for follow-up, while PET-CT should be part of follow-up. {Sun-395-H. P. Moreau}
  • Ph 2, n=100 pts, 25 per arm. Isatuximimab (SAR650984) single agent at different dose/frequencies: Arm 1: 3mg/kg every other week (q2w); Arm 2: 10mg/kg q2w for 4 doses, then q4w; Arm 3: 10mg/kg q2w; Arm 4: 20mg/kg qw x 4 dose then q2w. ORR: 9%, 20%, 29%, 24%. Gr 3 anemia in 20% of pts. {Mon-509-T. Martin}
  • A Medicare cost study was done for 3000 MM pts that assessed the economic burden for both MM treatment costs and pharmacy antiMM cost PPPM (cost per-patient per-month) for treatment lines First ($14K, $3K). Second ($16K, $3K), and Third ($16K, $3K) in 2015 dollars. Average treatment duration was 8, 6, and 5 mos respectively. {Sat poster-2100-C. Chen}
  • A study examined Cytogenetic (CG) Progression for 130 pts over the course of their disease, taking bone marrow samples and looking for risk factors such as del 17p, t(14;16), t(14;20), t(4;14), del 13 and gain 1q21. 90 (69%) of 130 pts had normal CG at diagnosis but 27% of these pts developed abnormal CG during disease course, resulting in shorter median OS (4 yrs) versus pts with normal CG (11.3 yrs) or even pts with any CG abnormality at diagnosis (7.4 yrs). Bone marrow biopsies/aspirates are important during the course of treatment. {Mon poster-4209-C. Pascal}
  • Palliative Care is a multidisciplinary approach to symptom management, psychosocial support, and assistance in treatment decision-making for both patients with serious illness and their families. Unlike Hospice, PC does not require either a terminal diagnosis or proximity to death.

In the US there are >6500 board-certified palliative medicine physicians and >18,000 certified non-physician palliative care professionals who work together with a patient’s other doctors to provide an extra layer of support. PC in the setting of SCT should be considered from the day of diagnosis and tied to need, not to prognosis. How do we balance the trade off in which life may be prolonged and cancer cured, but quality of life is poor? PC has particular relevance in oncology given recent studies which link PC to improved patient QOL, improved survival, and decreased cost of care.

 

SUMMARY

For someone diagnosed with stage III MM 21 years ago with only 2 treatment options available (MP or VAD-SCT) and given 2-3 years expected survival, I’ve seen incredible progress since 2000, and especially this past year 2015. While there continue to be unanswered questions, we now have many more effective treatments for MM, providing patients with better opportunities to manage their disease.

GLOSSARY (according to Jack)

Drug Class/Category

IMID – Immunomodulary Drug

PI – Proteasome Inhibitor

mAb – Monocloncal Antibody

Drugs (Brand Name)

C – Cyclophosphamide (Cytoxan)

Cfz – Carfilzomib (Kyprolis)

D – Daratumumab (Darzalex)

E – Elotuzumab (Empliciti)

I – Ixazomib (Ninlaro)

M – Melphalan

P – Prednisone

Pano – Panobinostat (Farydak)

Pom – Pomalidomide (Pomalyst)

R – (Lenalidomide) Revlimid

S – Isatuximab (SAR650984)

T – Thalidomide

V- Velcade (Bortezomib)

Treatment Success Measurements

EFS – Event-free Survival

ORR – Overall response (>=PR)

OS – Overall Survival

PD – Progressive Disease

PFS – Progression-free Survival

PFS2 – PFS + next-line treatment PFS

TTP – Time to Progression

TTR – Time to Respond

Treatment Response

CR – Complete Response: No sign of MM (0 M-spike)

nCR – Near CR (positive M-spike, may be same as VGPR)

MR – Marginal Response: 0-50% reduction in MM

PR- Partial Response: 50% reduction in MM

SD – Stable Disease i.e. no response but also not worse

sCR-Stringent CR: CR+ normal FLC & no clonal cells

VGPR – 90% reduction in MM

MRD – Minimum Residual Disease typically by Flow Cytometry (NGF) or DNA sequencing (NGS) to provide more accurate measure of MM.

Side Effects

AE (ASE) – Adverse Event (Adverse Side Effects)

DVT – Deep Vein Thrombosis (blood clots)

MTD – Maximum Tolerated Dose

ONJ – Osteonecrosis of the Jaw

PE – Pulmonary Embolism

PN – Peripheral Neuropathy

QOL – Quality Of Life

VTE – Venous Thromboembolism (PE + DVT)

Tests/When to treat?

CRAB – High Calcium, Renal, Anemia, and Bone…

CRABi – CRAB + “i” increased infections

FLC – Free Light Chain

SCT – Auto stem cell transplant.

“d” and “D” – Typically both mean Low-dose Dex (40 mg/week) these days

MGUS – Monoclonal Gammopathy of Undetermined Significance

SMM – Smoldering MM

Pt(s) – Patient(s)

R/R- Relapsed/Refractory Ref defined progressing while on Tx or within 60 days.