Day 3 – “Myeloma Monday” Saving the Best for Last

Jack Aiello |

Before providing details of our final full day at ASH (noting #abstract where applicable), let me review some activities from yesterday (Sunday 12/8/19). In the morning I attended a number of myeloma cancer care delivery abstracts (#383, #423, #424) where topics like diversity and racial/socioeconomic impact were discussed. Black/African-American patients are less likely to have transplants; but with treatment access at the Veterans Administration, they actually do better than their white counterparts. Perhaps, in small part, that could be because blacks, on average are diagnosed 3 years younger. However, because African-American baseline creatinine (kidney) levels are higher than whites, clinicians might misperceive renal function. This misperception could lead to reduced levels of Revlimid prescriptions (since Rev is secreted through the kidney). In one abstract example, the National Cancer Database for Myeloma patients diagnosed 2005-2015 concluded that there’s no overall survival (OS) difference between Medicare and private insurance patients.

(Note: Click links to the abstracts denoted to clarify drug names).

I attended some biology abstracts (#506, #507, #508, and #509) which presented potential new markers as targets for, say, prognosis and treatment. These included CD27- vs CD27+ T cells, ROBO1, PHF19, and Mutated Lymphopoiesis & B Cell Oligoclonality. I can’t tell you what they mean but am still happy to see research discussing new targets.

The rest of the day was spent meeting with various pharmaceutical companies such as Takeda, GSK, Karyopharm, and Amgen, (except Takeda), all of whom are relatively new to developing MM products and want to connect with patients so that they can provide better patient products and materials. Hopefully, they will continue to also sponsor the IMF, which provides so many patient services.

Now onto Myeloma Monday, which provided fascinating information about new products or treatment regimens. Here are just a few, which started at 7 a.m. and went till 7:30 p.m. Highlights included (# abstract number), and remember, unless otherwise noted, these immunotherapy treatments of CARs, Antibody Drug Conjugates (ADCs) and BiTEs are typically in trial for previously treated patients whose T-cells have been beat up:

CARTITUDE-1 (#577) is Janssen & Janssen’s U.S. version of China’s LEGEND-2 product. Called JNJ-4528, this CAR-T directed at BCMA has showed 27 of 29 patients’ progression-free after 6 months (it’s early), 1005 overall response rate (ORR) and good minimal residual disease-negativity (MRD-) results. However, all but 2 patients also experienced Cytokine Release Syndrome (CRS), which was typically controlled via tocilizumab and steroids.

A CD-19 and BCMA sequential CAR-T (#578) for 29 patients showed 86% ORR, 16 months median progression-free survival (PFS) and 2-yr overall survival (OS) of 56%. And one-third of patients were MRD- at 10-6

A long-term follow-up of  BCMA CAR-T from China denotes LCAR-B38M (#579) provided results for N=57 patients. ORR=88%, Complete Response (CR)=74%, med PFS was 20 months (but 28 months for CR patients) and median OS is 36 months (but Not Yet Reached for CR patients). One of the speaker’s patients had 5 prior lines of therapy and so far has PFS = 39 months.

For newly diagnosed multiple myeloma, several studies examine new regimens: 1) Griffin (#691): RVd +/- Dara -> SCT -> Consolidation and R +/- Dara maintenance. The Dara arms improved response rates and depth of response and after a relatively short time, 2-yr PFS and OS are 96% vs 89% and 98% vs 96% respectively; 2) Ixa-Dara-d in unfit and frail patients (#695), 23 each, showed median PFS of 23 and 12 months respectively.

For high-risk smoldering multiple myeloma (HR-SMM) patients, these were some studies: 1) An update on the CESAR study (#781) KRd -> SCT -> KRd -> Rd: ORR (CR) after induction 94% (43%), after stem cell transplant (SCT) 99% (63%), after consolidation 100% (73%) (N= about 90 patients). And at 35 months, PFS and OS are 92% and 96%; 2) Ixa-Rev-d: ORR 94%, 70% MRD- @ 10-6.

There were certainly more which I’ll pull together in a summary blog and my annual ASH write-up. In the meantime, you’ll want to view a replay of Monday night’s IMWG Conference Series that featured Drs. Brian Durie (Chairman of the Board, International Myeloma Foundation), Joseph Mikhael (IMF Chief Medical Officer), and Maria V Mateos (University of Salamanca, Spain).  Make sure to listen to the replay if you didn’t hear it live. It’s a great one-hour summary of ASH2019.

Wishing you the best of health!

— Jack Aiello, on Twitter @JackMAiello

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