Yes, today was the last full day of ASH but that’s not to say if wasn’t full of information with oral presentations packing the day from 7 a.m.–6 p.m. Highlights included these abstracts listed as follows (# abstract number):
- (#673) A 1200 pateint study showing benefit of an autologous stem cell transplant (ASCT) versus VMP (Velcade-Melphalan-Prednisone) in a regimen beginning with Velcade-cyclophosphamide-dexamethasone (VCD) induction and possible consolidation and maintenance. The SCT are had better three-year progression free survival (PFS) (65% vs 57%), which also held true for the high-risk multiple myeloma patients (three-year PFS 52% vs 42% and three-year overall survival 86% vs 75%). Stem cell transplant (SCT) still has a place in the multiple myeloma treatment arsenal.
- (#674) Ixazomib-Lenalidomide-Dexamethasone (IRd) (all oral therapy) before and after an SCT followed by Ixazomib maintenance resulted in a 44% complete response (CR). They may add daratumumab in the future.
- (#675) However, Kyprolis-Revlimid-dex before and after an SCT stole the show with 86% CR (and 81% CR for high-risk multiple myeloma). Three-year progression free survival and overall survival were 86% and 95%, respectively, and side effects were manageable. High MRD- rates by both Next Generation Flow (NGF) and Next Generation Sequencing (NGS), 97% and 71% respectively, showed an excellent depth of response. Let’s hope it’s sustainable over many years.
- (#973) Unlike yesterday, which showed Selinexor single agent activity, this abstract reported Phase 1 trial results for Selinexor + Carfilzomib + dex for high-risk multiple myeloma patients. In particular, Carfilzomib-refractory patients saw an overall response rate (ORR) of 67%, showing that Selinexor can overcome proteasome inhibitor resistance. (#977) This is the STOMP trial which combines Selinexor + Velcade/dex and saw ORR of 77% overall and 58% in proteasome-inhibitor-refractory patients.
- (#974) Remember that CAR-T patient on the front of Parade Magazine that indicated her multiple myeloma was cured with CAR-T therapy? Well, she did sustain a PFS of 16 months before relapsing, but now after using daratumumbab is in a subsequent twelve-month remission. Of the 12 patients, 5 others got into a very good partial response (VGPR) but have since relapsed. CAR-T treatment is exciting but still a very early treatment protocol.
- (#975) This abstract showed Venetoclax combined with Velcade/dex for patients with relapsed/refractory multiple myeloma. Overall response rate (ORR) was 67%, but Velcade non-refractory patients with 1-3 lines of prior therapy showed a 97% ORR.
- (#976) Elotuzumab plus lenalidomide-dex in high-risk smoldering multiple myeloma patients achieved 82% ORR for 23 pts, presumably resulting in delaying progression to symptomatic multiple myeloma, which would likely happen within a couple of years.
- (#1141) This trial for Newly Diagnosed MM pts examined Carfilzomib-Thalidomid-dex- > SCT -> Carfilzomib-Thalidomide-dex and saw a 95% ORR, including a 64% complete response. PFS and OS at three years was 68% and 90%, respectively. Interestingly, for high-risk patients, responses and ORR were about the same, but three-year PFS was wrose.
- (#1142) And another SCT trial for newly diagnosis multiple myeloma patients looked at Carfilzomib-Revilimid-dex for both induction and consolidation followed by Rev maintenance. Again, high response rates, stringent Complete Response was (sCR) was 57%, very good partial response (VGPR) was 91%, MRD- was 70% after consolidation.
- Finally, one ASH oral presentation I wasn’t able to attend discussed the use of daratumumab (Dara) given subcutaneously (subQ) rather than by the long five- to nine-hour long infusion. The subQ dosage recommendation is 90ml given over 30 minutes and so far both patient responses and side effects (mostly Infusion reactions the first time) are similar to infused Dara.
Monday night’s IMF IMWG Conference series featured Drs. Brian Durie (International Myeloma Foundation), Joseph Mikhael (Mayo Clinic, Scottsdale, Arizona), and Sagar Lonial (Emory, Atlanta) discussing “Making Sense of Treatment, 2016”. Here are some of their comments about ASH highlights although I’d really suggest watching a replay of this event which will be posted on the IMF website:
Dr. Brian Durie: Who should be treated and when, specifically referring to smoldering multiple myeloma (SMM) patients?
Dr. Sagar Lonial: We typically use the “gentle” (e.g. Rev or Rd) rather than “aggressive” (e.g. Dara-RVd plus SCT) approach because we don’t really know which high-risk smoldering multiple myeloma (SMM) patients will progress. . . some within a year and some are more like MGUS.”
Dr. Joseph Mikhael: “We could be ‘under’-treating them.”
Dr. Sagar Lonial: “For SMM, it’s more important to know the tempo of their disease rather than risk factors, which is why I have my SMM patients come in again for tests one month after their SMM diagnosis.”
Dr. Brian Durie: “For patients in a Complete Response, half with be MRD- and half with be MRD+.”
Dr. Joseph Mikhael: “Yes, and I’m also afraid that some might interpret MRD- as a cure, which is not true.” At least not until they have sustained MRD- without treatment for several years because they can relapse.
Well, that’s it for the last night of ASH. I’ll be blogging a summary that will include Tuesday’s final late-breaking abstract coverage [transplants for multiple myeloma patients] as well as create a PDF file with details of trial results and comments from ASH that I found interesting. Just email me firstname.lastname@example.org if you want the link.