Day 3 – Saving the Best for Last

Jack Aiello |

December 3, 2018

Yes, today was the last full day of ASH, but that’s not to say it wasn’t full of information with oral presentations packing the day from 7:00 a.m.–7:45 p.m. Highlights included (# abstract number):

  • Isatuximab-Vel-Rev-dex (Isa-VRd) for Newly Diagnosed Non-stem-cell-transplant-eligible myeloma patients (#595): This four-drug phase I study for 27 patients reported 100% of patients >= Very Good Partial Response (VGPR) with 7 of 16 evaluable patients achieving minimal residual disease negative status (MRD-)
  • Ninlaro (Ixazomib)-daratumumab—dex (IDd) for unfit & frail newly diagnosed multiple myeloma patients (#596): This phase II study report on the first 20 patients, where 10 of 10 unfit patients and 8 of 10 frail patients achieved overall response rate (ORR) respectively.
  • Selinexor-dex for penta-refractory (#598) and selinexor-dara-dex for patients previously exposed to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) (#599): Both showed excellent results (ORR 26% and 79% respectively) with manageable side effects, explaining why selinexor will likely be the next FDA-approved drug for the penta-refractory patients…who really need treatment help.
  • Melflufen (a different kind of alkylating agent) was given to patients who were triple-class refractory, for example, an IMID, PI and monoclonal antibody (mAb) (#600): For 82 patients, ORR was 33% (11% >=VGPR) and progression-free survival (PFS) was 6.4 months for those who achieved ORR.

CAR-T reports #955, #956, #957, #959, #960, #1009, #1011, #1012, #1013, #1014, and #1015 (plus others I wasn’t able to attend) all reported some benefit and variation in their CAR-T design.  However, the number of patients still seemed small to me (10-57 patients), and most still had varying dosages and different sensitivities of MRD, as well as median patient previous lines of therapies (3-11). Perhaps the most interesting abstract was #955 which was a CAR-T program from China that reported initial 12/12 success at ASCO. Now looking at 70 patients with median of 3 LOT (1-7), they reported 68% achieving MRD- and for those patients, median PFS was 24 months (6 months if you didn’t achieve MRD-).

Amgen’s AMG 420, a BiTE, connecting a multiple myeloma cell’s BCMA antigen with a T-cell’s CD3 receptor was given to 42 relapsed/refractory multiple myeloma patients (#1010): At the best-determined dose, 7 of 10 patients achieved ORR and 4 were MRD-. One concern, however, AMG 420 is given continuously via a pump for 4 weeks, then 2 weeks off, then 4 weeks, and so forth, for 10 of these 4-week pump infusions. However, I believe Amgen is working on a longer lasting BiTE that has a longer life not requiring continuous IV.

Monday night’s IMWG Conference Series featured Drs. Brian G.M. Durie (International Myeloma Foundation), Joseph Mikhael (IMF Chief Medical Officer), and María-Victoria Mateos (University of Salamanca, Spain) discussing Making Sense of Treatment, 2018.  Make sure to listen to the replay if your didn’t hear it live. It’s a great one-hour summary of ASH2018.

Wishing you the best of health!

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