Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma

Abstract

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1–45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159–0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454–0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR ( P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3–4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

Final analysis from RESONATE: Up to six years of follow‐up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma

“…The CR/CRi rates have increased over time with ibrutinib treatment, approaching a plateau beyond 3.5 years (9% and 11% with median 44 and 64 months of follow‐up, respectively). This is consistent with deepening of response with continuous ibrutinib therapy for responding patients and is similar to the improved responses observed over time with longer follow‐up in patients with relapsed/refractory CLL in the HELIOS study and in the phase 2 PCYC‐1102/1103 study . Notably, the proportion of patients who reported clinically meaningful improvement in FACIT‐F score was greater with ibrutinib than ofatumumab, and the improvement was maintained over time.…”

Observational evidence from patients diagnosed with chronic lymphocytic leukaemia (CLL) in Finland between 2005‐2015 show improved survival over time

“…20 Its evidence as second-line treatment is even more sparse, as the pivotal clinical study was a small single-arm phase 2 trial 21 and phase 3 studies have shown a poor effect of BR at relapse compared to novel agents. [22][23][24] Although a recent observational study concluded that BR is an effective salvage at first relapse, 25…”

A minimális reziduális betegség vizsgálata krónikus limfoid leukémiában

“…CLL kezelé sében az elmúlt években a másik rendkívül hatékony elsőnek választandó szer a Bruton-tirozin-kináz-(BTK-) gátló ibrutinib. Az ibrutinibkezelés hatékonyságát több klinikai vizsgálat is igazolta [19,20], azonban BTK-gátlás hatására az esetek többségében nem volt elérhető uMRD-szint [21]. Továbbá egy másik klinikai vizsgálat megmutatta, hogy nincs jelentős különbség az uMRD-és a dMRD-státuszú ibrutinibbel kezelt betegek túlélése között [22].…”