Tag Archive for: ASH15

Impatient Patients

The recent ASH (American Society of Hematology) meeting in Orlando focused on a host of new therapies for blood cancers and possible combinations of these new drugs that could forge paths to cures.

Leukemia, myeloma and lymphoma patients are grateful for the research and dedication from medical experts from around the globe.  But as I learned from talking to several, patients also are impatient. So they are taking action to move the research needle faster toward blood cancer cures.

David Wallace was diagnosed in 2009 with polycythemia Vera, an MPN or myloproliferative neoplasm.  He struggled to find precise, relevant information about PV, so he launched PV Reporter.  PV Reporter started as a hobby but has grown into a full-time endeavor.  David is educating thousands of patients and care partners about PV, namely that indeed it IS a cancer.  He said many patients are told PV is not a cancer, and they miss the opportunity to participate in clinical trials as well as programs to help fund peripheral needs such as transportation to and from the trial site.  David recently launched <mpncancerconnection.org> to complement PV Reporter.  David’s message:  If you have doubts about your diagnosis, find another doctor now, at a major research center if possible!

Then there is a Jenny Ahlstrom. Jenny’s been a multiple myeloma patient since 2010, nearly two years after her 6th child was born.  Jenny founded <myelomacrowd.org> which not only educates MM patients on the latest advances, but also is raising money for research to treat high risk myeloma. Jenny’s message to patients: Toward that end, Jenny has raised more than $150,000 (!) toward a goal of 1/2 million dollars (!) to fund two game-changing projects which harness the body’s immune system to knock back the disease.  Jenny’s message to us patients:  We patients CAN and SHOULD accelerate the pace of research toward a cure.  Want to do more than wait? Go to <myelomacrowd.org> to fund the research that will save lives.

Pat Killingsworth shouldn’t be alive.  Pat over nine years burned through multiple myeloma therapies faster than fire burns through paper.  A very somber Pat told me at ASH 2014 that he’d reached the end of the treatment road.  And yet there he was at ASH 2015-bald, thin, wearing a mask and SMILING after not one but two autologous (using his own stem cells) transplants! Read Pat’s story at <myelomablog.com>  Pat became ill after this year’s ASH, probably too many germs to combat at the Orlando Convention Center, but then a ‘miracle.’ The transplants worked. Pat was declared myeloma-free.  Pat is the model for never giving up, never taking ‘no’ for an answer and pushing back hard against adversity through education and action.  His will to live far outran the potentially lethal ravages of multiple myeloma.

Finally, Jack Aiello.  Many of you know Jack as a 21-year multiple myeloma survivor.  Through failed therapies, transplants and more treatments, Jack beat the odds. He survived MM when most patients died from it. Jack has turned his good fortune into activism.  He constantly learns about new therapies and, through the International Multiple Myeloma Foundation, educates patients to fight their disease.  Why work so hard for others when you’ve already beaten the disease?

These four delicious grandkids, including the newest Aiello born this month, came into Jack’s life long after his diagnosis.  Imagine if Jack hadn’t fought through the very difficult trials of treatment?

These four stories are but a smattering among hundreds – from patients who aren’t treading water and simply hoping for a cure.  They are the activists who are partnering with researchers to make it happen.  In their and our lifetimes.

Carol Preston was diagnosed with CLL in 2006, in remission for 5 1/2 years.

#ASH15 Interview with CLL Expert Dr. Jeff Sharman

Interview With Dr. Jeff Sharman, MD, Medical Oncologist, Willamette Valley Cancer Institute and Research Center Medical Director, Hematology Research, The US Oncology Network

In an exclusive interview at the 2015 American Society of Hematology (ASH) meeting, Dr. Jeff Sharman discusses the latest news on CLL treatment options for patients. Ibrutinib, a BTK inhibitor is discussed as a possible frontline treatment – the Resonate Study is mentioned. In a randomized phase 3 study, they were surprised at how well patients did on Ibrtinib monotherapy, which should lead to FDA approval. Dr. Sharman also talks about ABT-199, a BCL-2 inhibitor currently in clinical trials and the challenges that face treatment with these powerful drugs. Combination therapy and monotherapy are discussed, as are side effects and costs of therapy to the patient.

Dr. Sharman is hopeful about CLL treatment and closes with the statement, “Our patients with CLL, with rare exceptions, are going to be living much more normal lives than their counterparts just several years ago.” As always, knowledge is power. Having an active dialogue with your medical team will give you confidence and hope for whatever your CLL situation is.

Jeff Sharman, MD, Medical Researcher at US Oncology Network, Discusses CLL News for Patients from Patient Empowerment Network on Vimeo.

[toggle title=”Full Transcript Here” state=”closed”]

Andrew Schorr:

Hello. Andrew Schorr on location at the ASH meeting, American Society of Hematology, in Orlando. I’m with Dr. Jeff Sharman, a noted CLL expert and with US Oncology Network and also based in Oregon. Thank you so much for being with us, Jeff. Let’s talk about CLL news, okay? So we’ve had really some novel agents, and one of them, ibrutinib, has been followed. It’s been a big deal for people, but we’re trying to decide and study whether it has application earlier, so there was some news about that, right?

Dr. Sharman:

Yes. So reporting today will be the randomized RESONATE 2 study, which compares the efficacy of ibrutinib versus chlorambucil. Now, chlorambucil is hopefully never going to be studied again as a control arm in a study. This should‑‑

Andrew Schorr:

It’s an old medicine.

Dr. Sharman:

It’s an old medicine, and I think that now with the results of this study and a prior study with the addition of obinutuzumab, or Gazyva, we’ve now shown two studies with not only superiority in terms of progression‑free survival but both of these now report overall survival benefits compared to chlorambucil monotherapy. So as of today chlorambucil, done, no more.

Andrew Schorr:


Dr. Sharman:

Yeah. And it has been fading in North America for quite some time. But in terms of the results of this study, this was a randomized Phase 3 study, half patients of chlorambucil, half patients with ibrutinib, primarily in patients who would be considered appropriate for chlorambucil. Now, there was crossover allowed in this study, and this study started before ibrutinib was approved, and so I think that there were a number of patients who said, I’ll take chlorambucil, just so that they had a 50/50 chance knowing that if things didn’t go well they could then go on ibrutinib.

Ideally this is unique to those patients who are older with co‑morbidities or other medical issues that prevent them from getting aggressive chemoimmunotherapy type strategies, but regardless I think the most useful interpretation of this data isn’t so much the expected outcome that ibrutinib did better than chlorambucil but how well patients do on ibrutinib monotherapy.

This should lead to FDA approval of this drug in frontline. What we don’t know is how narrow or how broadly the FDA will construct that approval. That’s important because what the FDA writes in their guidelines and guidance is oftentimes what insurance will pay for, so‑‑and if they make it a challenge for insurance‑‑it really gets in all sorts of games, if you will. This study is in older patients who are considered inappropriate for chemotherapy, and that’s actually been a patient population for which idelalisib was approved with similar language.

So I think the devil will be in the details of the wording here, but it will introduce ibrutinib broadly or more broadly into the frontline treatment rather than restricted to those patients with 17p, as the label currently is formulated.

Andrew Schorr:

Okay. Now, other news here, a couple of others I wanted to talk about, one is about what had been ABT‑199 (?inaudible) letters of venetoclax, and its utility, and that seems to be coming along, and it seems to be a powerful drug.

Andrew Schorr:

Venetoclax is a very powerful drug in contrast to the B‑cell receptor signal inhibitors, so there‑‑the B‑cell receptor signaling pathway is a sequence of enzymes that help transmit biochemical signals within a CLL cell, and there are a sequence of these. And they include Btk, SIK, PI3 kinase and a variety of others, and there are probably two to five drugs for each of those targets.

But ibrutinib, idelalisib, duvelisib, entospletinib, you know, a variety of these targeted enzymes, those are B‑cell receptor signal inhibitors. In contrast, venetoclax is a Bcl‑2 inhibitor. Bcl‑2 is important for keeping one substructure within a cell arrive, what we call the mitochondria. Mitochondria is like the power generator of a cell, and what Bcl‑2 does is it keeps that power generator functioning. If you administer a Bcl‑2 inhibitor, that power generator goes into self‑destruct mode and takes the CLL cell out with it, and so we see instead of these kind of slow responses that transpire over many months and even years with the B‑cell receptor signal inhibitors, we see dramatic changes sometimes even after a single pill with the Bcl‑2 inhibitors.

Andrew Schorr:

Which is why for people in the trials they have to be monitored very carefully at the beginning.

Dr. Sharman:

Yeah. So, many of the studies that have looked at Bcl‑2 inhibitors have included mandatory hospitalizations for the administration of the drug. And so that’s how that going to translate into a drug that we would generally give as an outpatient I think remains to be seen and are some of the hurdles for that drug.

Andrew Schorr:

But a powerful drug.

Dr. Sharman:

Very powerful drug.

Andrew Schorr:

Okay. And so that gets us to clinical studies, and you discuss them all the time here. As you’re looking at combining drugs now, and that can be expensive. If these drugs get approved or are approved‑‑this is another insurance question maybe too‑‑but can that lower the likelihood that if you were taking let’s say ibrutinib by itself your cancer becomes resistant to it because you’re trying to hit the cancer cell multiple ways, down and out, right? And that maybe is the new horizon for CLL, right? Combinations?

Dr. Sharman:

Yeah. In oncology, the history of oncology has always been dominated by combination therapy. With rare exception the addition of other drugs leads to more cures than just one drug alone. Now, there are exceptions to that, but that is the nature of most‑‑the last 50, 60 years of oncology.

I think what patients want is the opportunity to have a very effective therapy that gets their disease into remission and not stay on therapy, and that’s where we wish to take the field. We’re not there yet. Currently, ibrutinib is once you start it you stay on it indefinitely, and there’s no end point.

Now, that’s okay in many regards because ibrutinib for most patients is a very well tolerated drug with acceptable side effects, but not for everybody. Joint pains, bruising bleeding, atrial fibrillation, there are a variety of reasons why some patients might be intolerant of ibrutinib. And in that regard if we can move the field towards shorter duration of therapy maybe that overcomes some of the cost limitations because if you start doing a Bcl‑2 inhibitor and a Btk inhibitor and maybe a CD20 antibody you could be talking very quickly about a half million dollars of therapy in aggregate cost, and that’s obviously unsustainable if that’s going to be done in perpetuity.

Andrew Schorr:

Okay. So we have economic questions. We have questions on how to outsmart the smart CLL cell. So just to wrap up, Jeff, you hear the news, you’re part of the news, and you’re seeing patients all the time. For people coming to you now and people out here and watching our video are you hopeful?

Dr. Sharman:

Oh, gosh, yeah. I mean, I think one of the sort of magical moments, if you will, of being a doctor is meeting that patient who’s been told they have some cancer and they don’t know much about it and walking them through those first hours of talking to an oncologist perhaps over several visits and watching this transformation from somebody who is very often understandably very alarmed to giving some hope for what’s out there that‑‑I think in a prior discussion we talked about average survival eight and a half years, you know, some of these statistics that are old, those statistics aren’t real anymore.

Our patients with CLL with rare exceptions are going to be living much more normal lives than their counterparts even just a few years ago.

Andrew Schorr:

Great. Wow. You know, that’s very exciting. I want to thank you for all you do.

Dr. Sharman:


Andrew Schorr:

Thank you for the hopeful news, and just remind all of you that, you know, it’s said all the time, it almost sounds trite, but it’s so true. Knowledge is power. Be a full partner in your care, consult with someone, a team that’s really knowledgeable in CLL, have an active dialogue. It will give you confidence, it will give you hope, and now you’re hearing that there are more and more tools to help you whatever your CLL situation is. We’ll keep you informed on Patient Power. Thank you for joining us.

From Orlando Florida and the ASH meeting, I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.


Myeloma Highlights from #ASH15

According to Jack Aiello (definitely not medically trained)


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.



  • 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



  • “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)



  • 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}



  • {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}



  • 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}



  • {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}



  • 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}



  • 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


  • 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.



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.



#ASH15 Hosts Discussion on Social Media

At the recent American Society of Hematology annual meeting, Joseph Mikhael, MD, MEd, FRCPC (@jmikhaelmd) hosted a panel discussion on the importance of social media . The panel included Michael A. Thompson, MD PhD (@MTMDPhD), Cindy Chmielewski, BA (@MyelomaTeacher),  Navheet S Majhail, MD, MS, (@BldCancerDoc), Laura C. Michaelis, MD, (@lauracmichaelis), Jeff Szer, MB, BS, FRACP, (@marrow), and Amber M. Yates, MD, (@sicklecelldoc).

The panel discussed how social media can be used for research, education, patient information and patient advocacy. The great advantage of using social media is that it is not demanding and its use is flexible. The individual can tailor it to suit his own needs.

The panel focused on the use of twitter and the benefits it provides in the healthcare industry. Twitter is an unique way to share information quickly, rapidly, in real time, and across borders.During the panel discussion, the twitter hashtag for the session, #ASHSM was trending on twitter and the twitter stream was running strong.

One panel member, Cindy Chmielewski had this to say about social media and twitter:

“Social Media is a tool in medicine that shouldn’t be overlooked.  It’s a source of education.  Social media has helped me evolve from a passive bystander to an active partner on my healthcare team.  I use social media to share resources and important information, promote myeloma awareness, advocate for cancer friendly public policies, form communities, but most importantly to learn.
Twitter is one of my classrooms and doctors who tweet are my teachers. The power of Twitter should not be underestimated.  If you educate one patient advocate you can reach thousands of other patients. Studies show that educated, empowered patients have the best possible outcomes. Isn’t that what we all want?  It’s a win-win situation.” 
Watch the video below to learn more about this important panel discussion on the use of social media in medicine.

Patient Advocacy – Views and Opinions at #ASH15

Twenty thousand people congregated in Orlando Dec 5th-8th for the annual American Society of Hematology meeting. A good number of them were patient advocates, from organizations all around the world. ASH did recognize these organizations and did give them a designated space on the exhibit floor, but did not give them free entry to the poster sessions, for instance, a practice that was criticized by some.

The Advocacy – Industry Relationship

The buzz at the meeting was that industry was becoming more and more amenable to partnering with these advocacy groups and to committing to try to understand the patient experience. The lunches and dinners and panel discussions that I attended were full of patient advocates who were conversing with the executives from pharmaceutical companies, answering their questions and themselves posing questions about the role of the patient in corporate decisions and strategy. At the Takeda Oncology Patient Advocate and Industry panel discussion, Fatima Scipione, Senior Director, Patient Advocacy for Takeda stated with conviction, “Patient impact is in everything we do.” Gail Sperling, Senior Manager, Information Resource Center at the Leukemia and Lymphoma Society, followed through with this concept by adding, “Pharma really values the patient voice because they realize how important it is.”

At the Genentech dinner talk, industry and executives discusses how collaboration between advocates and industry leaders benefits everyone. They talked about a patient-designed clinical trial that they had worked on and explained that how having patients participating from the outset really helped the overall trial outcomes.

Will this continue? Will it evolve? Hopefully it will and hopefully it will result in a clearer understanding by industry and providers of the patient’s crucial role in his own healthcare. There was a comment at the Takeda Patient Advocacy and Industry panel discussion that struck me –  “The relationship between patient advocacy and industry should be genuine and sustainable”. Let’s hope that this becomes the case.

How Can We Reach More Patients?

The patient advocates that attend ASH and other “Patients Included” medical meetings are extremely sophisticated in their knowledge of medical information and social media. They are confident individuals that are extremely web-savvy. They are members of various organizations and support groups for patients, and they have a “voice” online that is strong and respected. Other patients who are online listen to these POLs (Patient Opinion Leaders) and pay attention to what they say. And that is wonderful and so very helpful for them.

My question is this – How can patient advocacy organizations and POLs reach the patients that are NOT online? How can we go to patients that are not as tech-savvy or web-savvy and offer to help them find information about their illness, find help in support groups and get, perhaps, better care for themselves?

These patients would be the ones that are NOT being treated by a major cancer center. Nor would they belong to a patient community or support group. How can we reach them and introduce them to the strong online voices that we have in the patient advocacy community? Perhaps the older patients do not go online and are not savvy with social media or online patient support groups, but someone in their family surely is – their spouse, their children?

Should we reach out to families everywhere to ask them to advocate for their loved ones with cancer? Should we send out fliers to senior centers? Go through community organizations? All of the above? I don’t quite know the answer but I really would like to reach these patients.

ASH 2015 Annual Meeting

ASH 2015

The American Society of Hematology Annual Meeting will take place in Orlando, Florida from December 5 – 8, 2015. PEN will be covering this meeting with expert interviews and round table discussions with expert physicians and patient advocates. Please check back here for details. Thank you!

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