Samer Al Hadidi, Associate Professor at UT Southwestern Medical Center, shared a post on X:
“MonumenTAL-3
Published at NEJM
- RCT, phase 3: Tal-DP vs Tal-D vs DPd
- Treatment was until progression or intolerance (not time-limited)
- Early relapse ≥1 prior line including lenalidomide + PI ( no anti-CD38 refractory)
- allowed for T-cell redirecting >3 months
median FU ~ 2 yrs n=864 median age: 64 (range:30-88 yrs) median 2 prior lines (range 1–8) , ~1/3 had only 1 prior line ~12% prior daratumumab ~69% prior SCT
median treatment duration: ~22 months (Tal-DP), ~22 months (Tal-D), ~19 months (DPd) treatment discontinued: Tal-DP 30%, Tal-D 30% | DPd 53%, mainly progressive disease (13% vs 16% vs 40%) and adverse events (13% vs 8% vs 7%) treatment delays very common: 82% Tal-DP, 73% Tal-D, 55% DPd
median FU ~ 2 yrs ORR: Tal-DP 88%, Tal-D 89%, DPd 78% CR or better: Tal-DP 71.%, Tal-D 69%, DPd 35% 2-yr DOR: 86% (Tal-DP) vs 80% (Tal-D) vs 60% (DPd) MRD-neg CR (10⁻⁶): 48% (Tal-DP), 42% (Tal-D), 10% (DPd)
-yr PFS: Tal-DP 81%, Tal-D 78%, DPd 51% Median PFS not yet reached in either talquetamab arm vs ~2yrs in DPd 2-yr OS: Tal-DP 89%, Tal-D 88%, DPd 79% OS not different at interim analysis (pre specified alpha boundary was 0.0001)-likely will show at longer follow up.
Fatal AEs: Tal-DP 2% (n=5), Tal-D 4% (n=11),DPd 5% (n=13) Grade 3/4 neutropenia: Tal-DP 76%, Tal-D 29%, DPd 86% (questionable benefit of pomalidomide addition with significant increased myelosuppression) Grade 3/4 infections: 38% vs 29% vs 42%(Tal-D lowest) High rates of hypogammaglobulinemia (70–82%) requiring frequent IVIG.
Any grade taste change: Tal-DP 73%, Tal-D 75%, DPd only 4% (clearly related to Talq in RCT) discontinuation of talquetamab due to dysgeusia: 4% (Tal-DP) vs 2% (Tal-D) 58% resolved (42% didn’t) weight loss: Tal-DP 46%, Tal-D 38%, DPd only 7% (clearly related to Talq in RCT)-BMI decrease primarily in first 6 months then stabilized.
Ataxia/balance disorders: Tal-DP 15%, Tal-D 12%, DPd 0.4%. Onset is late: median ~292–326 days, increasing from cycle 7 onward (11% Tal-DP, 10% Tal-D)-Led to talquetamab discontinuation: 5% (Tal-DP) vs 2% (Tal-D) The major issue with it is that reversibility is poor: 88% Tal-DP and 68% Tal-D events not recovered/resolved at data cutoff with median duration ~107–108 days, imp table ICANS occurred in 3% (Tal-DP) vs 2% (Tal-D), all resolved.
Final thoughts
Excellent PFS benefit for non BCMA target: (HR ~0.28–0.33) Pom addition not needed IMO, Talq-Dara is enough for combination. More neutropenia with Tal-DP and also more 2nd primary malignancies with Tal-DP (8%) vs Tal-D (4%) vs DPd (4%) Taste changes in ~74%, often persistent( QoL impact)+weight loss ~38–46% Cerebellar/balance toxicity in ~13–15%, delayed onset, often not reversible (should we limit the use of Talq to 1 yr given delayed onset with longer use?-MonumenTAL-6 will be helpful) Field should move to time-limited therapy with such efficacious agents and work better to improve adverse events profile that may negatively affect QoL.”
Title: Talquetamab–Daratumumab in Relapsed or Refractory Myeloma
Authors: Roberto Mina, Meral Beksac, Paula Rodríguez-Otero, Wenming Chen, María-Victoria Mateos, Jian Li, Philippe Moreau, Yael C. Cohen, Chang-Ki Min, Tomas Jelinek, Jing Christine Ye, Hila Magen, Samuel M. Rubinstein, Weijun Fu, Vania Hungria, Guldane Cengiz Seval, Joao Samuel Farias, Jakub Radocha, Senem Maral, Mehmet Turgut, Youngil Koh, Daniel O’Leary, Jayr Schmidt Filho, Raymond Thertulien, Gang An, Shang-Yi Huang, Sebastian Grosicki, Agata Tyczyńska, Rahul Banerjee, Matthew J. Pianko, Joaquín Martínez-López,
Pawel Steckiewicz, Dai Maruyama, Kentaro Fukushima, Albert Oriol, Jordi Lopez Pardo, Hartmut Goldschmidt, Charlotte Pawlyn, Aurore Perrot, Elena Zamagni, Meletios A. Dimopoulos, Leo Rasche, Jaszianne Tolbert, William Terry, Christelle Courtoux, Xiao Liu, Sandra Y. Vasey, Kaitlyn Connors, Mariacristina Festa, Christoph Heuck, Angélique Langlois, Lisa O’Rourke, Jiangxiu Zhou, Xiang Qin, Jiashen Lu, Joy Gong, Diego Vieyra, Peter M. Voorhees
Read the full article on The New England Journal of Medicine (NEJM).
Other articles featuring Samer Al Hadidi on OncoDaily.
