Rituximab, cladribine, and cyclophosphamide (RCC) induction with rituximab maintenance in chronic lymphocytic leukemia: PALG ‐ CLL4 (ML21283) trial

Abstract

The study confirmed the high efficacy and acceptable safety profile of induction therapy with RCC and maintenance therapy with rituximab in previously untreated patients with CLL.

Prognostic markers in patients with chronic lymphocytic leukaemia on targeted therapy, chemoimmunotherapy with anti-CD20 monoclonal antibody: a systematic review and meta-analysis of prognostic factors

“…OS was not reached in both the rituximab and observation group due to shorter follow-up time Robak 2017 [ 42 ] 18 countries To investigate the potential of adding ofatumumab to FC to improve PFS in relapsed CLL Rai stage 0-II or stage III/IV No PFS; HR: 0.67 OS; HR: 0.78 Addition of ofatumumab to chemotherapy with FC improved PFS compared to FC alone in patients with relapsed CLL Dartigeas et al 2017 [ 45 ] Europe To compare maintenance treatment with rituximab vs. no further treatment to prolong PFS in treatment-naive and fit patients aged ≥ 65 years with CLL Binet stage B or C Yes PFS; HR: 0.55, OS; HR: 0.89 Maintenance therapy with rituximab improved 3-year PFS as compared to observation. OS was not reached in both groups at the time of analysis Robak et al 2018 [ 43 ] Europe To assess the effect of maintenance treatment with rituximab vs. no further treatment in previously untreated patients with progressive CLL Rai stage I-IV No PFS; HR: 0.418 A 3-year PFS was significantly longer in the maintenance arm compared to the observation arm Woyach et al 2018 [ 14 ] Americas To evaluate the efficacy of ibrutinib, either alone or in combination with rituximab in older patients with untreated CLL Intermediate to high-risk modified Rai stage disease No PFS/OS; HR: 1.06 There was no significant difference in 2-year PFS and OS between the two arms. Interactions between cytogenetics and effect of treatment on PFS were observed Seymour et al 2018 [ 40 ] Americas, Europe To evaluate the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory CLL Not stated No PFS; HR: 0.17, OS; HR: 0.48 Significantly higher rate of 2 year PFS with venetoclax plus rituximab than with a standard chemoimmunotherapy, with benefit observed in all su...…”

Diagnostic and therapeutic recommendations of the Polish Society of Haematologists and Transfusiologists and Polish Adult Leukemia Group-CLL for chronic lymphocytic leukemia in 2021

“…According to the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Center Network (NCCN), the risk of febrile neutropenia during FCR exceeds 20%, which is an indication for primary prophylaxis with granulopoiesis stimulating factors [37,38]. Although no randomized trials comparing FCR to RCC (rituximab, cladribine, cyclophosphamide) have been conducted so far, we believe that both regimens can be used alternatively [39]. Direct comparison of FC and CC did not reveal any differences in the effectiveness and toxicity of both regimens [40].…”

A network meta-analysis of maintenance therapy in chronic lymphocytic leukemia

“…All six trials presented low risk in selection and reporting bias domains. In terms of performance and detection bias, two double-blind design studies with low risk in blinding and domains focused on lenalidomide [25,26]; three openlabel design studies focused on rituximab [27,28,49]; and one open-label design study focused on ofatumumab [50]. PALG CLL4 study had high risk of attrition bias due to premature termination [49].…”

“…The mean age ranged from 57.3 to 71.7 years, whereas the median follow-up duration ranged from 17.9 to 47.9 months. Three trials enrolled patients who had received only first-line therapy [25,27,49], one trial enrolled patients who received at least two-lines of therapy [50], and the remaining two trials were mixed [26,28]. Among three rituximab maintenance trials, CLL 2007 SA trial [27] recruited patients in responses to completed FCR induction therapy; AGMT CLL-8a trial [28] included patients who had response to first-line or second-line rituximab-containing chemoimmunotherapy; PALG-CLL4 trial [49] focused on patients with rituximab, cladribine, and cyclophosphamide (RCC) induction and received subsequent maintenance with rituximab.…”