Newly identified sufferers with a number of myeloma could have greater MRD-negativity charges when handled with Tecvayli alone or with Revlimid.
Sufferers with newly identified a number of myeloma skilled sturdy scientific exercise when handled with Tecvayli (teclistamab) alone or together with commonplace Revlimid (lenalidomide) as upkeep remedy after induction and autologous stem cell transplantation (ASCT), examine outcomes have proven.
Preliminary outcomes from the protection run-in element of the part 3 MajesTEC-4/EMN30 trial have been offered at the 2024 ASH Annual Assembly. Of observe, a security run-in a part of a trial is a preliminary part designed to evaluate the protection of a brand new remedy earlier than it strikes into larger-scale research.
The protection run-in consisted of three upkeep cohorts: two administering Tecvayli-Revlimid (cohorts 1 and a couple of) and one administering Tecvayli monotherapy (cohort 3). The primary distinction behind cohorts 1 and a couple of is that the Tecvayli dosing was much less intense in cohort 2.
The minimal residual illness (MRD)-negativity fee (10-5 sensitivity) was 100% amongst evaluable sufferers in all three cohorts. This was measured at 12 months in cohort 1 and at six months in cohorts 2 and three. Evaluable sufferers consisted of these with a baseline pattern and not less than one pattern throughout upkeep. The median progression-free survival (PFS) had not been reached in any of the cohorts.
“Unprecedented efficacy was noticed, with all evaluable sufferers attaining MRD negativity,” mentioned presenting creator Dr. Elena Zamagni, affiliate professor of hematology on the Bologna College, Italy.
Zamagni additionally reported that responses to remedy deepened throughout upkeep in all three cohorts. All sufferers in cohort 1 achieved an entire remission (CR) or higher, as did 90.6% of sufferers in cohort 2 and 93.3% of sufferers in cohort 3. In cohort 1, the CR fee was 9.4% and the stringent CR (sCR) fee was 90.6%. In cohort 2, 9.4% of sufferers achieved an excellent partial response (VGPR), 25% of sufferers achieved a CR, and 65.6% of sufferers achieved an sCR. The corresponding charges have been 6.7%, 23.3% and 70%, respectively, in cohort 3.
Relating to hematologic toxicity, probably the most incessantly occurring treatment-emergent hostile occasion (TEAE, aspect impact) was neutropenia. Throughout all time factors, the general fee of grade 3 (extreme)/4 (life-threatening) neutropenia was 93.8% in cohort 1, adopted by 62.5% in cohort 2, and 46.7% in cohort 3.
Zamagni additional defined, “If we take a look at the cumulative incidence of grade 3/4 neutropenia at six months, we are able to see that the incidence decreased considerably from 81% in cohort 1 — which had a extra intense [Tecvayli] dosing schedule — right down to 56% in cohort 2 and 40% in cohort 3.”
Zamagni added that, “Febrile neutropenia, anemia and eosinophilia have been very uncommon, as was the speed of remedy discontinuation as a result of TEAEs, which was low at 5.3% general.”
With nonhematologic TEAEs (excluding an infection), grade 3/4 TEAEs have been uncommon, with probably the most incessantly occurring being cytokine launch syndrome (CRS), which occurred in roughly half of the sufferers general. Most CRS circumstances occurred throughout Tecvayli step-up dosing, with 37.2% occurring after step-up dose 1, 8.5% occurring after step-up dose 2, and 5.3% occurring after remedy dose 1. There have been no circumstances of grade 3/4 CRS and no discontinuations as a result of CRS. Additionally of observe, there have been no circumstances of immune effector cell–related neurotoxicity syndrome. “We additionally had some diarrhea, primarily associated to [Revlimid], and a few injection website response,” added Zamagni.
Incidents of infections and hypogammaglobulinemia have been frequent, in accordance with Zamagni. Grade 3/4 infections occurred in 37.5%, 28.1%, and 20% of cohorts 1, 2 and three, respectively. The commonest infections have been higher respiratory tract infections, COVID-19, pneumonia and nasopharyngitis. Hypogammaglobulinemia occurred in 96.9%, 78.1% and 93.3% of cohorts 1, 2 and three, respectively. All of those sufferers obtained not less than one dose of intravenous or subcutaneous immunoglobulin. An infection prophylaxis was additionally strongly really useful.
Design and Demographics of the Security Run-In of MajesTEC-4/EMN30
There have been two Tecvayli-Revlimid cohorts and one single-agent Tecvayli cohort within the security run-in. In cohort 1 (32 sufferers), sufferers obtained Tecvayli at 1.5 mg/kg weekly for cycles 1 and a couple of, after which 3 mg/kg each two weeks for cycles 3 to six, and thereafter 3 mg/kg month-to-month for as much as two years of fixed-duration upkeep. For cohort 2 (32 sufferers), Tecvayli was given at 1.5 mg/kg on days 8 and 15, after which instantly after it was given at 3 mg/kg month-to-month. Within the single-agent cohort 3 (30 sufferers), the dose of Tecvayli was the identical as in cohort 2. For sufferers additionally receiving Revlimid (cohorts 1 and a couple of), Revlimid was initiated at 10 mg/day in 28-day cycles from cycles 2 to 4. If Revlimid was properly tolerated, the dose may very well be raised to fifteen mg/day for cycles 5 to 26. All sufferers have been scheduled to obtain fixed-duration upkeep for 2 years; nonetheless, for sufferers receiving Tecvayli-Revlimid who have been not less than in CR at one yr, Tecvayli was stopped.
General, 81 (86.2%) of the 94 randomized sufferers remained on remedy as of September 2024. Negative effects (5 sufferers) and affected person withdrawal (three sufferers) have been the 2 predominant causes for discontinuation. There have been two sufferers who discontinued as a result of progressive illness. Cohort 1 began earlier and thus had an extended median follow-up of 21.1 months. The median follow-up was 9.2 months for each cohorts 2 and three.
Design of Major MajesTEC-4/EMN30 Randomization
The outcomes of the protection run-in now inform the primary randomization part of the part 3 MajesTEC-4/EMN30 Trial.
The MajesTEC-4/EMN30 trial is enrolling sufferers with newly identified a number of myeloma with an ECOG efficiency standing of 0 to 2, who’ve obtained 4 to 6 cycles of a triplet or quadruplet induction remedy (PI and/or IMiD with or with out an anti-CD38 antibody) and a single or double ASCT with or with out consolidation. Sufferers should have not less than a partial response following these preliminary remedies.
The enrollment objective is 1,500 sufferers. Sufferers can be randomized evenly to fixed-duration upkeep remedy with Tecvayli-Revlimid, Tecvayli alone or Revlimid alone.
The MajesTEC-4/EMN30 trial is actively recruiting sufferers.
Reference
“Part 3 Examine of Teclistamab (Tec) in Mixture with Lenalidomide (Len) and Tec Alone Versus Len Alone in Newly Recognized A number of Myeloma (NDMM) As Upkeep Remedy Following Autologous Stem Cell Transplantation (ASCT): Security Run-in (SRI) Outcomes from the Majestec-4/EMN30 Trial” by Dr. Elena Zamagni et al., Blood.
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