Al-Ola A Abdallah, Associate Professor at the University of Kansas Medical Center, shared on X:
“CANOVA Phase III results are here! Venetoclax-dexamethasone pomalidomide-dexamethasone in patients with t(11;14)-positive relapsed/refractory multiple myeloma.
What did we learn?”
Title: ©Venetoclax-Dexamethasone Versus. Pomalidomide-Dexamethasone in t(11;14)-Positive. Relapsed/Refractory Multiple Myeloma: Primary Results of the Randomized, Phase III CANOVA Study
Authors: Rakesh Popat, Meral Beksac, Meletios A Dimopoulos, Moshe E Gatt, Francesca Gay, Jae-Cheol Jo, Prashant Kapoor, Eirini Katodritou, K Martin Kortüm, Silvia Ling, Chandramouli Nagarajan, Kenshi Suzuki, Lugui Qiu, Maika Onishi, Grace Ku, Monique Dail, Nabanita Mukherjee, Jeremy A Ross, Mohamed Ali Badawi, Mary Jean Fusco, Edyta Dobkowska, Emma Arriola, Orlando F Bueno, Nizar J Bahlis, Shinsuke Iida, Philippe Moreau, Jason Valent, María-Victoria Mateos
Read The Full Article
Why venetoclax?
t(11;14) myeloma demonstrates increased BCL-2 dependence, providing a strong biologic rationale for targeted BCL-2 inhibition with venetoclax. CANOVA tested whether this precision approach could outperform Pom-Dex.
Study design:
- Phase III, open-label trial
- 263 patients with ≥2 prior lines
- Ven-Dex: 133 patients
- Pom-Dex: 130 patients
- Primary endpoint: independently assessed PFS
Primary endpoint:
Median PFS:
- Ven-Dex: 9.9 months
- Pom-Dex: 5.8 months
- HR 0.823; P=0.24
Despite a numerical improvement of 4.1 months, the difference was not statistically significant.
Responses clearly favored Ven-Dex:
- ORR: 62% vs 35%
- ≥VGPR: 39% vs 14%
- MRD negativity: 8% vs 0%
Median OS was also numerically longer:
- 32.4 vs 26.9 months.
Additional findings were interesting:
- Time to next treatment: 21.2 vs 8.3 months
- Post hoc EFS: 9.4 vs 4.0 months
- EFS HR: 0.651
Differential censoring and earlier initiation of new therapy in the Pom-Dex arm may have complicated the PFS analysis.
Safety remains important:
Grade ≥3 adverse events:
- Ven-Dex: 67%
- Pom-Dex: 83%
However, fatal infections occurred in 7 patients receiving Ven-Dex and none receiving Pom-Dex. Low baseline CD4 counts may identify a particularly vulnerable population.
Bottom line:
CANOVA did not meet its primary PFS endpoint, so Ven-Dex cannot be considered a routine standard based on this trial.
However, the higher and deeper responses reinforce the biologic activity of BCL-2 inhibition in t(11;14) myeloma and support further development using better combinations, patient selection, and infection prevention.”
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