December 13, 2022

ASH 22 Reactions - GEM-CESAR

December 13, 2022

ASH 22 Reactions - GEM-CESAR

Author

Abstract # 118: María Victoria Mateos presented post-hoc analysis from the P2 GEM-CESAR trial in 90 patients with high-risk smoldering myeloma (SMM).GEM-CESAR assessed induction and consolidation chemotherapy with carfilzomib, lenalidomide and dexamethasone before and after melphalan and autologous stem cell transplant (ASCT), respectively, followed by lenalidomide and dexamethasone maintenance.

Results:

  • At median 65.8 mos, 94% of pts were alive and progression-free: 6 pts progressed to MM and 7 pts died
  • In same time frame, 31 patients had progressed to measurable residual disease; PFS at 5 years was 72%
  • Of the seven patient deaths:
    • Three progressive disease related
    • 1 cardiac arrest (not treatment-related)
    • 1 ischemic stroke
    • 1 lung cancer
    • 1 MDS
  • Sustained negative measurable residual disease 23% at 4 years post-ASCT

Thought leader reactions were largely negative, with several strongly condemning the death of asymptomatic patients in this trial:

Samer
Samer
Aaron
Samer
Amar

Carfilzomib, lenalidomide and dexamethasone (KRd) protocol with ASCT was not considered to be the most efficacious treatment for asymptomatic SMM:

Samer
Rahul
Manni
Samer

One thought leader raised concerns regarding a misdiagnosed patient population, and significant AEs:

Samer
Samer
Samer
Samer
Samer

Summary: Some thought leaders were critical of the GEM-CESAR trial, as asymptomatic patients suffered AEs(including deaths) for minimal benefit. While some commentators found the data more useful than others, theconsensus was that the carfilzomib, lenalidomide and dexamethasone protocol with ASCT is not to be used in asymptomatic patients with high-risk smoldering myeloma.

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Not rated
Allison Betof Warner, MD, PhD (she/her) 4
3743
Manhattan, NY
November 10, 2022

79% had reduction in disease. ORR 31%. Many responses deepen over time.

Not rated
Allison Betof Warner, MD, PhD (she/her) 3
3743
Manhattan, NY
November 10, 2022

Median DOR not yet reached. Median OS 13.9 mo. 12 mo OS was 54%. As typical with immunotherapy, we see a nice tail on the curve. #TIL#SITC22

Positive
Alex Shoushtari, MD
2253
New York, USA
November 10, 2022

Important work on efficacy of TIL therapy lifileucel in PD-1 resistant #melanoma being presented at #SITC22. Pretty good durability for this heavy lift of a treatment.

Not rated
Allison Betof Warner, MD, PhD (she/her) 2
3743
Manhattan, NY
November 10, 2022

Toxicity profile was in line with prior TIL/Lifileucel data. No surprises here. Median # doses of IL-2 was 6.

Positive
Hussein Tawbi, MD, PhD
1685
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November 10, 2022

Absolutely agree!… this should be available to our melanoma patients ASAP!… and paves the way for smarter cellular therapies to be designed, studied, and eventually widely disseminated

Positive
Allison Betof Warner, MD, PhD (she/her) 1
3744
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November 10, 2022

Where does this leave us with #TIL therapy for #melanoma? IMO, this response rate/durability justifies accelerated approval. Pts with PD-1 refractory melanoma need options. It’s FAR from a perfect tx but provides meaningful clinical benefit. What say you melanoma Twitterverse?

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Just before I start AM clinic at @cityofhopeoc, excited to share results from #COBALT_RCC, a P1 trial of @CRISPRTX#CTX130 in #kidneycancer in the @sitcancer#PressProgram. Will present more on Thurs 5:37p at #SITC22! Thx @neerajaiims@DrBenTran@HaanenJohn#SamerSrour& co-Is! t.co/aDnhG9n92A

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November 8, 2022
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CAR-Ts are coming for #kidneycancer!! Congratulations @montypal and team; can’t wait to see results at #SITC22! t.co/9MrlF2yzBe

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Congrats @montypal and team! Great to see CAR T therapy coming to #RCCt.co/ypRHBC89Pt

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Another huge step from none other than @montypal!! CAR-Ts in #kidneycancer!Congratulations to the entire team!Looking forward to seeing the results at #SITC22! t.co/HvKeVBPyV7

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