Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Bispecific antibody, still with toxicity though, although pts had pretreatment with obinutumzumab to mitigate CRS. Response rate 35% in pts who received CAR-T therapy.
CLL/SLL is usually characterized by consecutive relapses and response to therapy ultimately dictates survival. While ibrutinib, a first-generation Bruton tyrosine kinase inhibitor (BTKi), has become standard therapy, it has well-described off-target effects that can limit use. Compared with ibrutinib, zanubrutinib, a next-generation BTKi, provides improved BTK occupancy across disease-relevant tissues with greater kinase selectivity. In a randomized phase 3 study (ALPINE; NCT03734016), zanubrutinib was compared head-to-head with ibrutinib as treatment for R/R CLL/SLL. At predefined response analyses, zanubrutinib demonstrated superior overall response rate (ORR); data from the predefined final PFS analysis are reported here.
Patients (pts) with R/R CLL/SLL who had received ≥1 prior therapy and had measurable disease were randomized 1:1 to receive zanubrutinib or ibrutinib until disease progression or unacceptable toxicity. Stratification was based on age, refractory status, geographical region, and del(17p)/TP53 mutation status. As the primary endpoint of ORR was superior with zanubrutinib, the key secondary efficacy endpoint of PFS was tested for noninferiority under hierarchical testing when 205 PFS events were observed. If PFS noninferiority between zanubrutinib and ibrutinib was demonstrated, superiority of zanubrutinib vs ibrutinib could be tested and claimed if the 2-sided P-value was <.04996. Other endpoints included overall survival (OS), ORR including PR with lymphocytosis (PR-L) or better, and safety parameters including atrial fibrillation/flutter.
Pts (N=652) from 15 countries were randomized to receive zanubrutinib (n=327) or ibrutinib (n=325). Demographic and disease characteristics were balanced between zanubrutinib and ibrutinib arms (age ≥65 yrs [61.5 vs 61.5%]; male [65.1 vs 71.4%]; unmutated IGHV [73.1 vs 73.5%]; del(17p) [13.8 vs 15.4%]; TP53 mutated without del(17p) [9.2 vs 7.7%]). Across the study population, median age was 67 and 68 yrs, respectively; in both arms, median prior lines of therapy was 1.
As ALPINE is the first study to demonstrate PFS superiority in a head-to-head comparison of BTK inhibitors, zanubrutinib has now proven superiority to ibrutinib in both ORR and PFS in pts with R/R CLL/SLL. Efficacy benefits with zanubrutinib were observed across all major subgroups, including high-risk pts. Zanubrutinib had a favorable safety profile compared with ibrutinib, with a lower rate of treatment discontinuation and fewer cardiac disorder events, including fewer cardiac events leading to death. These data suggest zanubrutinib is more efficacious and better tolerated than ibrutinib as treatment for R/R CLL/SLL.
Bispecific antibody, still with toxicity though, although pts had pretreatment with obinutumzumab to mitigate CRS. Response rate 35% in pts who received CAR-T therapy.
The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone.
This is not a randomized study, results though can not be ignored since ibrutinib is less toxic than many of the treatments used.
Confirming that RR can be an alternative to R chemotherapy as a first line therapy in advanced stage follicular lymphoma.
This is a nice historical accounting of this sometimes-challenging paradigm. No randomized, prospective trials exist to guide practice management. The question in clinic is often, when to use prophylaxis and when not? The CNS-IPI is the best scoring system validated in the Rituximab era. This did not account for double/triple hit genetics, ABC subtypes or sites of disease (gonads, >3 sites). A high score or any of these groups are generally those that benefit the most from CNS-prophylaxis. The field has moved away from IT-MTX therapy to HD-IV-MTX since most secondary CNSL is parenchymal in nature. Most relapses occur at months 6-9 so sooner is probably better in terms of timing.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
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