Contributions
Abstract: EP800
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Lenalidomide plus rituximab is now a standard-of-care option for indolent B-cell non-Hodgkin lymphomas (iNHL) and mantle cell lymphomas (MCL). We previously demonstrated the efficacy of combination lenalidomide and rituximab in patients (pts) with rituximab-refractory iNHL and MCL (Chong et al Clin Can Res 2015). We now report the longest experience to date with this regimen.
Aims
The aim of this retrospective review was to determine 5 and 10-yr outcomes for rituximab-resistant pts treated with lenalidomide and rituximab and to identify adverse events (AEs) leading to dose discontinuation.
Methods
We conducted an open-label phase II trial in pts with iNHL or MCL and rituximab resistance, defined as failure to respond to or progression of disease within 6 months of rituximab or a rituximab-containing regimen. Pts received lenalidomide 10 mg daily for 8 weeks, followed by 4 weekly doses of rituximab 375 mg/m2 and continued lenalidomide maintenance until disease progression, toxicity or pt choice.
Results
50 pts (30 FL, 14 MCL, 2 MZL, 4 SLL) were enrolled between 2008-2012. Median follow-up was 10.5 years (yr). Pts received a median of 3 prior therapies (range: 1–7). Progression free survival (PFS) for all pts at 5 and 10 yrs was 20.0% [95%CI 8-35] & 13% [95%CI 3-30%]; 5- and 10-yr response duration (RD) was 27% [95% CI 12-46] and 18% [95% CI 4-40], respectively; 5- and 10-yr overall survival (OS) was 58% [95%CI 43-70] and 45% [95%CI 30-58], respectively. 5-yr OS from the time pts were deemed rituximab-resistant was 64.0% and 10-yr OS 51.9%.
For pts with FL, 5- and 10-yr PFS were both 13%, and 5- and 10-yr OS were 60% and 40%. For MCL, 5- and 10-yr PFS were both 25% and 5- and 10-yr OS were 50% and 36%. At 10.5 yr follow-up, 4 pts (2 FL, 1 MCL, 1 MZL) remain in complete remission (CR), 3 of whom discontinued lenalidomide at 7.0-yr, 8.8-yr and 10.1-yr in CR. 1 pt with FL discontinued study in CR after 11.6-yr but continues on commercial lenalidomide at 5 mg daily.
The most common grade 1–2 AEs requiring dose reductions were neuropathy (n = 3) and diarrhea (n = 5), which all resolved with dose reduction. The most common grade 3–4 AEs requiring dose reductions were neutropenia (n = 6, 12%) and tumor flare (n = 3, 6%). Pts discontinued therapy due to toxicity at a median of 4.9 mo (range 0.3–25.7) from lenalidomide start due to grade 3–4 rash (n = 2), grade 2 abdominal pain (n = 1), and grade 3–4 thrombocytopenia (n = 2). Only 1 pt discontinued lenalidomide after >1 yr (25.7 mo); this was due to persistent diarrhea. The pt who developed grade 2 abdominal pain was retreated with lenalidomide without recurrence of pain and sustained a second CR for 5 yrs. 5 (10%) pts developed secondary cancers at a median of 15.5 mo (range: 0.8–50.5) from starting lenalidomide, including 2 hematological (acute myeloid leukemia, B-acute lymphoblastic leukemia) and 3 solid cancers (NSCLC, renal cell carcinoma, prostate cancer). Prior to enrollment, 4/5 of the pts with secondary cancers had received alkylating agents and 3/5 had received anthracyclines. Of all pts, 78% had previously received alkylating agents and 62% had received anthracyclines.
Conclusion
These data represent the longest reported outcomes for lenalidomide plus rituximab in iNHLs and MCL. We demonstrate durable responses and a manageable safety profile with rituximab plus low-dose lenalidomide.
Keyword(s): Lymphoma, Rituximab
Abstract: EP800
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
Lenalidomide plus rituximab is now a standard-of-care option for indolent B-cell non-Hodgkin lymphomas (iNHL) and mantle cell lymphomas (MCL). We previously demonstrated the efficacy of combination lenalidomide and rituximab in patients (pts) with rituximab-refractory iNHL and MCL (Chong et al Clin Can Res 2015). We now report the longest experience to date with this regimen.
Aims
The aim of this retrospective review was to determine 5 and 10-yr outcomes for rituximab-resistant pts treated with lenalidomide and rituximab and to identify adverse events (AEs) leading to dose discontinuation.
Methods
We conducted an open-label phase II trial in pts with iNHL or MCL and rituximab resistance, defined as failure to respond to or progression of disease within 6 months of rituximab or a rituximab-containing regimen. Pts received lenalidomide 10 mg daily for 8 weeks, followed by 4 weekly doses of rituximab 375 mg/m2 and continued lenalidomide maintenance until disease progression, toxicity or pt choice.
Results
50 pts (30 FL, 14 MCL, 2 MZL, 4 SLL) were enrolled between 2008-2012. Median follow-up was 10.5 years (yr). Pts received a median of 3 prior therapies (range: 1–7). Progression free survival (PFS) for all pts at 5 and 10 yrs was 20.0% [95%CI 8-35] & 13% [95%CI 3-30%]; 5- and 10-yr response duration (RD) was 27% [95% CI 12-46] and 18% [95% CI 4-40], respectively; 5- and 10-yr overall survival (OS) was 58% [95%CI 43-70] and 45% [95%CI 30-58], respectively. 5-yr OS from the time pts were deemed rituximab-resistant was 64.0% and 10-yr OS 51.9%.
For pts with FL, 5- and 10-yr PFS were both 13%, and 5- and 10-yr OS were 60% and 40%. For MCL, 5- and 10-yr PFS were both 25% and 5- and 10-yr OS were 50% and 36%. At 10.5 yr follow-up, 4 pts (2 FL, 1 MCL, 1 MZL) remain in complete remission (CR), 3 of whom discontinued lenalidomide at 7.0-yr, 8.8-yr and 10.1-yr in CR. 1 pt with FL discontinued study in CR after 11.6-yr but continues on commercial lenalidomide at 5 mg daily.
The most common grade 1–2 AEs requiring dose reductions were neuropathy (n = 3) and diarrhea (n = 5), which all resolved with dose reduction. The most common grade 3–4 AEs requiring dose reductions were neutropenia (n = 6, 12%) and tumor flare (n = 3, 6%). Pts discontinued therapy due to toxicity at a median of 4.9 mo (range 0.3–25.7) from lenalidomide start due to grade 3–4 rash (n = 2), grade 2 abdominal pain (n = 1), and grade 3–4 thrombocytopenia (n = 2). Only 1 pt discontinued lenalidomide after >1 yr (25.7 mo); this was due to persistent diarrhea. The pt who developed grade 2 abdominal pain was retreated with lenalidomide without recurrence of pain and sustained a second CR for 5 yrs. 5 (10%) pts developed secondary cancers at a median of 15.5 mo (range: 0.8–50.5) from starting lenalidomide, including 2 hematological (acute myeloid leukemia, B-acute lymphoblastic leukemia) and 3 solid cancers (NSCLC, renal cell carcinoma, prostate cancer). Prior to enrollment, 4/5 of the pts with secondary cancers had received alkylating agents and 3/5 had received anthracyclines. Of all pts, 78% had previously received alkylating agents and 62% had received anthracyclines.
Conclusion
These data represent the longest reported outcomes for lenalidomide plus rituximab in iNHLs and MCL. We demonstrate durable responses and a manageable safety profile with rituximab plus low-dose lenalidomide.
Keyword(s): Lymphoma, Rituximab