Ben Derman, Assistant Professor at University of Chicago, shared a post on X:
“My top 11 myeloma/amyloidosis abstracts I’m excited about, spanning bispecifics, CAR T, MRD and amyloid clearance. Stay tuned for a much longer discussion at the end re: MajesTEC-3…
1) Abstract 94 (Luciano J Costa): CARTITUDE-4 Long-term PFS with cilta-cel in standard-risk patients showed a 30-month PFS rate of 71% (ITT) and 80.5% (as-treated). It would be good to know the breakdown by lines of therapy. We need to continue having conversations with patients about cilta-cel as early as second line as we find ways to reduce delayed toxicities.
2) Abstract 99 (Dytfeld): Disclosure I am an author. The phase 3 COBRA trial compared weekly KRd x 24 cycles vs. VRdx8/Rdx16. Longer course of KRd makes complicates direct comparison but…VRd is hard to administer for long periods of time due to neuropathy (whereas K can be easier).
Higher rates of MRD<10^-5 with KRd; PFS also longer with KRd. No difference in OS at this time.
With dara potentially being used in smoldering and/or with MajesTEC-3 showing tec/dara in relapse works well, could the KRd backbone be useful into the future?
3) Abstract 248 (Diko Kazandjian): Could consolidation with a bispecific antibody supplant transplant? IMMUNOPLANT is a ph2 study enrolling patients with MRD positivity after 4+ cycles of induction.
Patients received 4-6 cycles of linvoseltamab before maintenance.
MRD conversion to negativity was the primary endpoint. 14/14 (100%) converted to MRD<10^-6. None of the 19 pts thus far had CRS/ICANS.
If a short course of Bsab can lead to lasting/durable MRD negativity, this will be a very exciting development that could be another nail in the coffin for transplant. Could additional cycles of quad therapy further decrease the need for this regimen?
4) Abstract 256 (Krina Patel): iMMagine-1 – Anito-cel BCMA CAR T in triple-class exposed RRMM. PFS rate at 18-months 66% which compares mostly favorably with others. No IEC-enterocolitis or atypical neurologic toxicities seen thus far.
Most important thing at this point is long-term outcomes.
5) Abstract 258 (Du et al.): GC012F/AZD0120 in newly diagnosed myeloma following 2 cycles of VRd. This dual-targeting BCMA/CD19 FasTCAR led to a 30-month PFS of 88% and 82% sustained MRD negativity, which ranks among the best of outcomes in newly diagnosed MM!
Clearly we are headed toward frontline BCMA-directed therapies – the question is which one and for whom?
6) Abstract 269 (Richard et al.): DURGA-1 study with AZD0120 – same product in RRMM.
Median time from apheresis to release 14 days and vein-to-vein 28 days. Only 1.4 months follow-up but among 15 evaluable patients, ORR 100% and all MRD evaluable patients were MRD<10^-5. 75% CRS (mostly grade 1). Highly efficacious and prior data suggests toxicity is low.
7) Abstract 697 (Robert Z. Orlowski): Ph1 LINKER-MM4. Linvo monotherapy +/- transplant. Transplant eligible patients received limited duration linvo; ineligible patients received linvo until progression.
ORR 79% but 86% at the 50-200 mg doses. 52% MRD negativity by ITT. No progression events or deaths. 44% CRS. 31% grade 3-4 infections.
Need longer follow-up, but could monotherapy be the way to go for transplant-ineligible patients?
8) Abstract 693 (Bell et al.): AT-02 in AL amyloidosis. A pan amyloid-binding Ig fusion that theoretically removes deposits. Not just turning off the spigot, but cleaning up the mess!
Enrolled patients with at least a VGPR (i.e., already responded hematologically) but had GFR <90. In the q2week group, GFR increased by 16 and proteinuria improved in one patient (no benefit in q4week).
Is this a real signal? Or is this delayed renal response? I like the study design (patients in response) and think this is how we might want to approach amyloid removers.
9) Abstract 919 (Gonzalez et al.): Peripheral residual disease by ultra-sensitive BloodFlow (circulating tumor cells at 10^-7) and Mass Spec in GEM2017FIT.
Among patients who were double-negative PRD, only 5% were MRD positive in BM. Only 4% of patients with 24-month sustained PRD negativity progressed. Less invasive MRD/PRD continues to evolve!
10) LBA1: KLN-1010 (Ho et al.): in-vivo CAR T is coming fast and furious. Here we have (very) preliminary but encouraging results from 3 patients treated with an LD-chemo-free in-vivo-CAR T KLN-1010. The premise is to modify endogenous T-cells to become BCMA-directed CAR T cells.
All patients reached MRD <10^-5 by month 1.
Brisk lymphocytosis is seen (up to 43×10^9L in one patient) – remains to be seen what are the long-term outcomes and toxicities.
11) LBA3: MajesTEC-3 (B): Tec-Dara vs Dara-Pd/Dara-Vd
Patients with 1-3 prior lines and without prior anti-CD38 refractoriness or BCMA exposure were randomized to Tec-Dara vs DPd/DVd. Tec went to q2weeks for cycles 3-6, and q4weeks thereafter.
Clear and substantial PFS benefit to Tec-Dara (HR 0.10) with 3-year PFS of 83.4%! This is the best outcome we have seen in any trial in this population. At least as good as as-treated standard-risk CARTITUDE-4, albeit apples to oranges. 54% grade 3+ infections worth noting.
We don’t have data yet on composition of patients: len refractoriness, anti-CD38 exposure, high-risk features (will need to see presentation). Particularly interested in how high-risk patients performed and prior anti-CD38 exposure. Also treatment-related deaths not shown.
This is really going to change the way we think about every newer therapy in myeloma and will create a major ripple effect for all therapies in development, especially BCMA-directed ones. Soon we might have two highly effective options for 1+ prior lines.
- If new drugs are studied in early line settings, will they enroll well?
- If new BCMA-directed or immunotherapies are studied in later line settings, will patients even be eligible and will the results be relevant by the time they are reported?”
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