DURABLE RESPONSES WITH IDELALISIB MONOTHERAPY IN PATIENTS (PTS) WITH RELAPSED OR REFRACTORY MARGINAL ZONE LYMPHOMA (MZL)
(Abstract release date: 05/19/16)
EHA Library. Gyan E. 06/09/16; 134776; PB1876
E Gyan
Contributions
Contributions
Abstract
Abstract: PB1876
Type: Publication Only
Background
MZL is a group of indolent non-Hodgkin lymphomas (iNHL) arising from marginal zone B cells in lymph nodes and/or extranodal tissues, is classified per the World Health Organization as splenic MZL (SMZL), nodal MZL (NMZL) and extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue; MALT). Given the rarity of MZL, few randomized trials have directly compared treatment options. Thus, there is a lack of consensus about best practices. Idelalisib (IDELA) showed considerable anti-tumor activity in pts with relapsed/refractory (R/R) iNHL in a phase 1 (P1) dose-escalation study (NCT00710528; Flinn, 2014) and in pts with refractory iNHL in a phase 2 (P2) study (NCT01282424; Gopal, 2014).
Aims
The objective of this post hoc analysis was to describe the safety and efficacy of IDELA in a subset of pts with MZL.
Methods
The P1 and P2 studies were single-arm monotherapy trials that assessed safety and efficacy of idelalisib in R/R hematologic malignancies (P1) or iNHL (P2). Eligible pts with MALT, NMZL or SMZL were those with R/R disease (disease status defined by response to last prior regimen) in the P1 study and those with double-refractory disease (to both rituximab and an alkylating agent) in the P2 study. IDELA was given as monotherapy (P1: minimum dose 50 mg BID, maximum dose 350 mg BID; P2: 150 mg BID) until progressive disease (PD), death or unacceptable toxicity. Radiographic and pertinent clinical data were reviewed by an independent review committee (IRC) to determine the response based on standard criteria for lymphomas (Cheson et al. J Clin Oncol. 2007;25;579-586).
Results
In all, 21 pts with MZL were enrolled, 6 in the P1 and 15 in the P2 study: 12 with MALT, 7 with NMZL and 2 with SMZL. Median age was 74 and 72 yrs [range 50-91], and 50% and 80% were male, in the P1 and P2 studies, respectively. Pts had received a median of 4.5 prior regimens in the P1 study [range 1-10] and a median of 2 prior regimens in the P2 study [range 2-9]. The median (range) IDELA exposure was 5 mo (0.4-16.4) and 6.4 mo (1.8-21.6) in the P1 and P2 studies, respectively. In the P1 study, Gr≥3 adverse events (AEs) occurring in ≥20% of pts included diarrhea (3/6), and chills, fatigue, pyrexia, urinary tract infection and dizziness (each 2/6); key Gr ≥3 laboratory abnormalities occurring in ≥20% of pts included thrombocytopenia (4/6), and anemia, neutropenia, and ALT and AST increases (each 2/6). In the P2 study, Gr≥3 diarrhea and Gr≥3 neutropenia laboratory abnormalities each occurred in 3/15 pts. Of the 21 pts, 9 (43%) achieved a response. Outcomes by MZL subtype are shown in the table. Median times to first response were 1 mo and 3.5 mo in the P1 and P2 studies, respectively. In the P1 study, the median duration of response (DOR) was 8.2 mo, and in the P2 study 18.4 mo. In the P1 study, with median follow-up time of 5 mo, median progression free survival (PFS) was 7.4 mo; in the P2 study, with median follow-up time of 20 mo, median PFS was 6.6 mo. Overall Survival (OS) was 100% at 1 yr in the P1 study, and in the P2 study was 86% at 6 mo, 79% at 9 mo, and 72% at 1 yr.
Conclusion
Although the sample size was small, IDELA showed promising activity in pts with R/R MZL. IDELA was well tolerated with no apparent disease-specific safety signals.
Session topic: E-poster
Keyword(s): Indolent non-Hodgkin's lymphoma, Marginal zone
Type: Publication Only
Background
MZL is a group of indolent non-Hodgkin lymphomas (iNHL) arising from marginal zone B cells in lymph nodes and/or extranodal tissues, is classified per the World Health Organization as splenic MZL (SMZL), nodal MZL (NMZL) and extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue; MALT). Given the rarity of MZL, few randomized trials have directly compared treatment options. Thus, there is a lack of consensus about best practices. Idelalisib (IDELA) showed considerable anti-tumor activity in pts with relapsed/refractory (R/R) iNHL in a phase 1 (P1) dose-escalation study (NCT00710528; Flinn, 2014) and in pts with refractory iNHL in a phase 2 (P2) study (NCT01282424; Gopal, 2014).
Aims
The objective of this post hoc analysis was to describe the safety and efficacy of IDELA in a subset of pts with MZL.
Methods
The P1 and P2 studies were single-arm monotherapy trials that assessed safety and efficacy of idelalisib in R/R hematologic malignancies (P1) or iNHL (P2). Eligible pts with MALT, NMZL or SMZL were those with R/R disease (disease status defined by response to last prior regimen) in the P1 study and those with double-refractory disease (to both rituximab and an alkylating agent) in the P2 study. IDELA was given as monotherapy (P1: minimum dose 50 mg BID, maximum dose 350 mg BID; P2: 150 mg BID) until progressive disease (PD), death or unacceptable toxicity. Radiographic and pertinent clinical data were reviewed by an independent review committee (IRC) to determine the response based on standard criteria for lymphomas (Cheson et al. J Clin Oncol. 2007;25;579-586).
Results
In all, 21 pts with MZL were enrolled, 6 in the P1 and 15 in the P2 study: 12 with MALT, 7 with NMZL and 2 with SMZL. Median age was 74 and 72 yrs [range 50-91], and 50% and 80% were male, in the P1 and P2 studies, respectively. Pts had received a median of 4.5 prior regimens in the P1 study [range 1-10] and a median of 2 prior regimens in the P2 study [range 2-9]. The median (range) IDELA exposure was 5 mo (0.4-16.4) and 6.4 mo (1.8-21.6) in the P1 and P2 studies, respectively. In the P1 study, Gr≥3 adverse events (AEs) occurring in ≥20% of pts included diarrhea (3/6), and chills, fatigue, pyrexia, urinary tract infection and dizziness (each 2/6); key Gr ≥3 laboratory abnormalities occurring in ≥20% of pts included thrombocytopenia (4/6), and anemia, neutropenia, and ALT and AST increases (each 2/6). In the P2 study, Gr≥3 diarrhea and Gr≥3 neutropenia laboratory abnormalities each occurred in 3/15 pts. Of the 21 pts, 9 (43%) achieved a response. Outcomes by MZL subtype are shown in the table. Median times to first response were 1 mo and 3.5 mo in the P1 and P2 studies, respectively. In the P1 study, the median duration of response (DOR) was 8.2 mo, and in the P2 study 18.4 mo. In the P1 study, with median follow-up time of 5 mo, median progression free survival (PFS) was 7.4 mo; in the P2 study, with median follow-up time of 20 mo, median PFS was 6.6 mo. Overall Survival (OS) was 100% at 1 yr in the P1 study, and in the P2 study was 86% at 6 mo, 79% at 9 mo, and 72% at 1 yr.
| Best Overall Response, n | CR | PR | SD | PD |
| MALT | 1 | 4 | 6 | 1 |
| NMZL | 0 | 2 | 4 | 1 |
| SMZL | 0 | 2 | 0 | 0 |
Conclusion
Although the sample size was small, IDELA showed promising activity in pts with R/R MZL. IDELA was well tolerated with no apparent disease-specific safety signals.
Session topic: E-poster
Keyword(s): Indolent non-Hodgkin's lymphoma, Marginal zone
Abstract: PB1876
Type: Publication Only
Background
MZL is a group of indolent non-Hodgkin lymphomas (iNHL) arising from marginal zone B cells in lymph nodes and/or extranodal tissues, is classified per the World Health Organization as splenic MZL (SMZL), nodal MZL (NMZL) and extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue; MALT). Given the rarity of MZL, few randomized trials have directly compared treatment options. Thus, there is a lack of consensus about best practices. Idelalisib (IDELA) showed considerable anti-tumor activity in pts with relapsed/refractory (R/R) iNHL in a phase 1 (P1) dose-escalation study (NCT00710528; Flinn, 2014) and in pts with refractory iNHL in a phase 2 (P2) study (NCT01282424; Gopal, 2014).
Aims
The objective of this post hoc analysis was to describe the safety and efficacy of IDELA in a subset of pts with MZL.
Methods
The P1 and P2 studies were single-arm monotherapy trials that assessed safety and efficacy of idelalisib in R/R hematologic malignancies (P1) or iNHL (P2). Eligible pts with MALT, NMZL or SMZL were those with R/R disease (disease status defined by response to last prior regimen) in the P1 study and those with double-refractory disease (to both rituximab and an alkylating agent) in the P2 study. IDELA was given as monotherapy (P1: minimum dose 50 mg BID, maximum dose 350 mg BID; P2: 150 mg BID) until progressive disease (PD), death or unacceptable toxicity. Radiographic and pertinent clinical data were reviewed by an independent review committee (IRC) to determine the response based on standard criteria for lymphomas (Cheson et al. J Clin Oncol. 2007;25;579-586).
Results
In all, 21 pts with MZL were enrolled, 6 in the P1 and 15 in the P2 study: 12 with MALT, 7 with NMZL and 2 with SMZL. Median age was 74 and 72 yrs [range 50-91], and 50% and 80% were male, in the P1 and P2 studies, respectively. Pts had received a median of 4.5 prior regimens in the P1 study [range 1-10] and a median of 2 prior regimens in the P2 study [range 2-9]. The median (range) IDELA exposure was 5 mo (0.4-16.4) and 6.4 mo (1.8-21.6) in the P1 and P2 studies, respectively. In the P1 study, Gr≥3 adverse events (AEs) occurring in ≥20% of pts included diarrhea (3/6), and chills, fatigue, pyrexia, urinary tract infection and dizziness (each 2/6); key Gr ≥3 laboratory abnormalities occurring in ≥20% of pts included thrombocytopenia (4/6), and anemia, neutropenia, and ALT and AST increases (each 2/6). In the P2 study, Gr≥3 diarrhea and Gr≥3 neutropenia laboratory abnormalities each occurred in 3/15 pts. Of the 21 pts, 9 (43%) achieved a response. Outcomes by MZL subtype are shown in the table. Median times to first response were 1 mo and 3.5 mo in the P1 and P2 studies, respectively. In the P1 study, the median duration of response (DOR) was 8.2 mo, and in the P2 study 18.4 mo. In the P1 study, with median follow-up time of 5 mo, median progression free survival (PFS) was 7.4 mo; in the P2 study, with median follow-up time of 20 mo, median PFS was 6.6 mo. Overall Survival (OS) was 100% at 1 yr in the P1 study, and in the P2 study was 86% at 6 mo, 79% at 9 mo, and 72% at 1 yr.
Conclusion
Although the sample size was small, IDELA showed promising activity in pts with R/R MZL. IDELA was well tolerated with no apparent disease-specific safety signals.
Session topic: E-poster
Keyword(s): Indolent non-Hodgkin's lymphoma, Marginal zone
Type: Publication Only
Background
MZL is a group of indolent non-Hodgkin lymphomas (iNHL) arising from marginal zone B cells in lymph nodes and/or extranodal tissues, is classified per the World Health Organization as splenic MZL (SMZL), nodal MZL (NMZL) and extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue; MALT). Given the rarity of MZL, few randomized trials have directly compared treatment options. Thus, there is a lack of consensus about best practices. Idelalisib (IDELA) showed considerable anti-tumor activity in pts with relapsed/refractory (R/R) iNHL in a phase 1 (P1) dose-escalation study (NCT00710528; Flinn, 2014) and in pts with refractory iNHL in a phase 2 (P2) study (NCT01282424; Gopal, 2014).
Aims
The objective of this post hoc analysis was to describe the safety and efficacy of IDELA in a subset of pts with MZL.
Methods
The P1 and P2 studies were single-arm monotherapy trials that assessed safety and efficacy of idelalisib in R/R hematologic malignancies (P1) or iNHL (P2). Eligible pts with MALT, NMZL or SMZL were those with R/R disease (disease status defined by response to last prior regimen) in the P1 study and those with double-refractory disease (to both rituximab and an alkylating agent) in the P2 study. IDELA was given as monotherapy (P1: minimum dose 50 mg BID, maximum dose 350 mg BID; P2: 150 mg BID) until progressive disease (PD), death or unacceptable toxicity. Radiographic and pertinent clinical data were reviewed by an independent review committee (IRC) to determine the response based on standard criteria for lymphomas (Cheson et al. J Clin Oncol. 2007;25;579-586).
Results
In all, 21 pts with MZL were enrolled, 6 in the P1 and 15 in the P2 study: 12 with MALT, 7 with NMZL and 2 with SMZL. Median age was 74 and 72 yrs [range 50-91], and 50% and 80% were male, in the P1 and P2 studies, respectively. Pts had received a median of 4.5 prior regimens in the P1 study [range 1-10] and a median of 2 prior regimens in the P2 study [range 2-9]. The median (range) IDELA exposure was 5 mo (0.4-16.4) and 6.4 mo (1.8-21.6) in the P1 and P2 studies, respectively. In the P1 study, Gr≥3 adverse events (AEs) occurring in ≥20% of pts included diarrhea (3/6), and chills, fatigue, pyrexia, urinary tract infection and dizziness (each 2/6); key Gr ≥3 laboratory abnormalities occurring in ≥20% of pts included thrombocytopenia (4/6), and anemia, neutropenia, and ALT and AST increases (each 2/6). In the P2 study, Gr≥3 diarrhea and Gr≥3 neutropenia laboratory abnormalities each occurred in 3/15 pts. Of the 21 pts, 9 (43%) achieved a response. Outcomes by MZL subtype are shown in the table. Median times to first response were 1 mo and 3.5 mo in the P1 and P2 studies, respectively. In the P1 study, the median duration of response (DOR) was 8.2 mo, and in the P2 study 18.4 mo. In the P1 study, with median follow-up time of 5 mo, median progression free survival (PFS) was 7.4 mo; in the P2 study, with median follow-up time of 20 mo, median PFS was 6.6 mo. Overall Survival (OS) was 100% at 1 yr in the P1 study, and in the P2 study was 86% at 6 mo, 79% at 9 mo, and 72% at 1 yr.
| Best Overall Response, n | CR | PR | SD | PD |
| MALT | 1 | 4 | 6 | 1 |
| NMZL | 0 | 2 | 4 | 1 |
| SMZL | 0 | 2 | 0 | 0 |
Conclusion
Although the sample size was small, IDELA showed promising activity in pts with R/R MZL. IDELA was well tolerated with no apparent disease-specific safety signals.
Session topic: E-poster
Keyword(s): Indolent non-Hodgkin's lymphoma, Marginal zone
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