Today was the final full day of ASH, and I attended oral presentations this morning beginning at 7 a.m. With all the excitement about recent multiple myeloma drug approvals last month, I wondered what might be next. The answer might be a drug called Pembrolizumab (Pembro), an anti PD-1 antibody that is also referred to as a checkpoint inhibitor. Early trials, Pembro + Revilmid/dexamethasone (Rd) and Pembro + pomalidomide (POMB) for relapsed/refractory multiple myeloma (RRMM) patients showed an overall response rate (ORR) of 56% and 60%, respectively. That’s quite high considering these patients had many previous treatments.
I also heard a presentation on Darzalex (daratumumab), which was just approved. The most fascinating part of this presentation was Dr. Torben Plesner (Denmark) speaking about being the first doctor to treat an MM patient with Dara in 2007! Another trial highlighting the drug SAR650984 (now called Isatuximab) was presented by Dr. Tom Martin (University of California, San Francisco). It also shows single-agent activity with ORR, ranging from 20% to 29% depending on the dosage arm, and will be moving to a phase 3 trial. And trials that resulted in Empliciti (elotuzumab) and Ninlaro (ixazomib) being approved were also presented. I found it interesting that Isatuximab/Revlimid/dexamethasone showed a median progression free survival (PFS) of about 21 months, whether a patient had the del 17p high-risk factor or not. And adverse events are essentially the same as Revilmid-only. And another new drug Filanesib (a kinesin spindle protein inhibitor) was paired with Carfilzomib (Cfz) as opposed to Carfilzomib-alone. In a Phase 2 trial for heavily pre-treated MM patients, ORR was 24% as opposed to 28% (only 4 percentage points better with Filanesib); however, progression free survival improved from 3.7 months to 8.5 months—so we’ll see.
Earlier this year, results of the ENDEAVOR trial comparing Cfz-dex (Kd) versus VELCADE/dexamethasone (Vd ). For example, when comparing proteasome inhibitors head to head, the results showed a median PFS of 19 months as opposed to 9 months, favoring the Kd arm. Today’s results were analyzed comparing each for patients with one prior line of therapy (PFS 22 months as opposed to 10 months) and >= 2 prior lines (PFS 15 months as opposed to 8 m months)—to summarize, the amount of previous treatment really matters. The same was true for ORR (1 line: 82 vs 66% and >= 2 lines: 72 vs 60%). And there was a talk discussing KRd vs Rd for RRMM high-risk patients [t(4:14), t(14:16), or del 17p]. Median PFS was 23 months as opposed to 14 months (versus standard risk 30 months as opposed to 20 months), and ORR was 79% vs 60% (versus standard risk 91% vs 74%).
Finally, I was involved in three other activities: 1) attending a session of Patient Reported Outcomes (PRO’s): ask your doc if you fill out PRO’s and, if so, how it is used; 2) an FDA-led meeting where the three FDA doctors who approved Darzalex (daratumumab), Ninlaro (ixazomib), and Empliciti (elotuzumab) respectively, presented the trials that resulted in the approval of these drugs. Then, Dr. S. Vincent Rajkumar (Mayo Clinic-Rochester) and Dr. Paul Richardson (Dana-Farber Cancer Institute, Boston) discussed how they would possibly use these drugs for frontline treatment (off-label but clinical trial preferred) and RRMM patients, respectively. Because it appears Rev-dex is the backbone treatment, many current and future combinations are VRd, KRd, DaraRd, IxaRd, and EloRd; 3) and I had the opportunity to spend a half hour interviewing myeloma experts Drs. Noopur Suresh Raje (Massachusetts General), Faith Davies (Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences), and community hematologist Dr. John Burke (Rocky Mountain Cancer Centers). I asked them a number of questions as pertained to the myeloma excitement we’ve seen at ASH.
Monday night’s IMF ASH event featured a webinar of Drs. Brian Durie (International Myeloma Foundation), Paul Richardson (Dana-Farber Cancer Institute, Boston), Joseph Mikhael (Mayo Clinic, Scottsdale, Arizona), and Antonio Palumbo (University of Torino, Torino, Italy) discussing “Making Sense of Treatment, 2015”. Here are some of their thoughts, but you should go HERE at the IMF website and listen to a replay yourself:
Dr. Durie: There was close to 800 MM abstracts, with over 20 focused on minimal residual disease (MRD). Is MRD ready for primetime?
Dr. Mikhael: We’re not ready for MRD in the clinic, but we’re ready to incorporate it into clinical trials to learn how MRD informs us of future treatment.
Dr. Palumbo: There’s no question that MRD is a prognostic factor like complete response (CR). But we need studies to determine how MRD values should change treatment. Plus, we still need to incorporate PET-CT imaging when we learned that in one trial of MRD- pts, 20-30% were found to be positive by PET-CT.
Dr. Durie: What’s the best frontline therapy for stem cell transplant (SCT)-eligible patients?
PR: VRd seems to have been confirmed as we best frontline treatment.
AP: VCd (also known as CyBorD) is another option, but a three-drug regimen is most important. However, I think we need to add consolidation after the SCT of 2-4 more cycles.
JM: For our high-risk patients, we consider giving KRd. But otherwise, it’s VRd. In fact, this is a change to Mayo’s M-SMART algorithm.
BD: And frontline for non-SCT eligible pts?
AP: Still VCd without the SCT.
JM: Rd only is acceptable for frail patients.
PR: RVd-LITE for frail patients.
Other questions were asked about relapsed-refractory patients (not as clear as newly diagnosed), the need for new drug categories, and which agents do you consider most promising. However, I’ll need to listen to the replay as well because I got tired and sort of zoned out.
Well, that’s it for tonight. I’ll be blogging a summary that will include tomorrow’s final abstract coverage [CAR-T (BCMA) for MM pts] as well as create a Word file with details of trial results and comments from ASH that I found interesting. Just email me [email protected] if you want a copy.
by Jack Aiello