Today was the final day of ASH, but it was still full of information, and to be honest, I’m a bit brain-fried. For me, the day started with an excellent Education Spotlight session on “Underrepresented minorities in clinical trials…”. It was chaired by multiple myeloma expert Dr. Ken Anderson and included talks from Drs. Luciano Costa and Sikander Ailawahdi. Why is this so important? Dr. Costa said, “Proper clinical trial population representation is necessary for both internal and external validity.” If Black people are twice as likely to get multiple myeloma as white people and represent 20% of myeloma cases but < 5% of multiple myeloma trial participants, then our trial results may not be externally valid.

How do we fix this? It will be difficult. Dr. Costa showed a slide that indicated income levels and NCI centers, which run trials are not necessarily in Black population areas. Many potential strategies were suggested by Dr. Ailawahdi (e.g. setting targets, updated inclusion criteria, pre-specify race subgroup analysis, community engagement, expanding trial locations, and more). Dr. Ailawahdi noted, “As more expensive niche multiple myeloma drugs come out, disparity may increase [so we need to do something sooner rather than later].” The area of diversity had more than a dozen abstracts focus on this difficult but necessary-to-fix issue.

Now to some of the other abstracts:

  1. Results of the 2-yr ASCENT trial (Dara-KRdx12-> DaraRx12 maintenance) for high-risk smoldering multiple myeloma (HR SMM) N=87 patients were updated. 55% of patients have completed the full 2 years while 14% of patients went off study for reasons like personal/physician decision, adverse events, progression, and 1 death. ORR is 97%, 84% have become minimal residual disease-negative (MRD-), and three-year progression free survival (PFS) is 90%. So, are any of these patients cured? They’ll need to be followed for 10-15 years before that question can be answer. [S Kumar, See ASH Abstract 757.]
  2. For Ultra HRMM (>1 HR factor or SKY92 genomic risk) and primary plasma cell leukemia patients, this treatment includes a transplant followed by 18(!) cycles of Dara-VR/d consolidation before DR maintenance till progression in a study called OPTIMUM. Results were favorably compared with ultra HR patients from the Myeloma XI trial with less, but still substantial treatment. For example, looking at about 100 comparable patients in each study, the PFS estimate at the end of consolidation (that’s 30 months) was 78% compared with 30-month PFS of 40% in Myeloma XI. And while results are early, 30 months overall survival (OS) is positive early at 84% v 74%. Prevention of relapse remains the key challenge for ultra HR, even for those that become MRD-. [M Kaiser, See ASH Abstract 758.]
  3. Another HRMM study for both transplant-eligible (stem cell transplant included) and transplant non-eligible (no stem cell transplant) that used Isa-KRd for induction, consolidation (4 v 6 cycles), and Isa-KR maintenance of 26 cycles. For N=99 and 26 patients respectively, ORR rates were 95% and 89%. However, PFS data wasn’t provided so there’s certainly more to learn. [K Weisel, See ASH Abstract 759.]
  4. A retrospective analysis comparing VRd with KRd induction for HRMM using 67 and 87 patients respectively from Memorial Sloan Kettering Cancer Center. The groups were well-balance, each having about 74% 1 HR factor and 26% >1 HR. ORR at the end of induction was 93% and 98% for VRd and KRd respectively. mPFS were 41 and 71 months while 5 year overall survival (OS) was 63% and 85% respectively. [CTan, See ASH Abstract 752.]
  5. The original KarMMa study which resulted in ABECMA approval showed a mPFS of 9 months. This new retrospective study examined pts getting ABECMA after prior BCMA treatment, which was not allowed in the KarMMa study. As such, for these prior BCMA treated patients, mPFS was only 3.2 months. [C Ferreri, See ASH Abstract 766.]
  6. There was a whole session (6 oral presentation abstracts 865-870) that focused on new approaches (e.g. BloodFlow, QIP-Mass-spec-Exent) to MRD testing, including new techniques to use peripheral blood and hopefully reduce the number of bone marrow biopsies.
  7. For the KarMMa study, it was shown that MRD- and complete response at months 1, 3, 6, and 12 correlate to improvement in mPFS of 12.5, 20, 22, and 30 months respectively. [B Paiva, See ASH Abstract 868.]
  8. MRD2STOP is the name of a study that examines patients after 1 year of maintenance therapy and enter this study to further examine PET and MRD- at both 10-6 and prospective 10-7 assessment. Of the 70 patients screened, 38 patients (39% with HR MM) met these negativity criteria and have stopped maintenance. After 15 months, 33 patients have had no MRD progression. It was also noted that over $9M is saved by stopping Rev maintenance after 15 mos. Of course, longer follow-up is needed. [B Derman, See ASH Abstract 870.]

Well, that’s it for 2022 ASH, although I feel there are topics that need to be more completely shared such as genomics, diversity, nutrition, frailty, and more. Fortunately, I know there will be webinars offered by the wonderful myeloma advocacy organizations that help us stay informed about myeloma. This “virtual” hybrid platform worked for the most part, though I do miss connecting face-to-face with others. I hope this will happen at the 2023 ASH conference in San Diego.

Be your own best patient advocate.

— Jack Aiello, on Twitter @JackMAiello