Idelalisib plus rituximab boosts survival in relapsed chronic lymphocytic leukemia

NEW ORLEANS – Adding idelalisib to rituximab significantly extends survival in patients with heavily pretreated relapsed chronic lymphocytic leukemia unsuitable for chemotherapy, according to results from Study 116.

The primary endpoint of median progression-free survival (PFS) was 5.5 months with rituximab (Rituxan) plus placebo and had not been reached with rituximab plus idelalisib (hazard ratio, 0.15; P less than .0001).

The PFS advantage was seen across all subgroups including patients with the 17p deletion and TP53 mutations, Dr. Richard R. Furman reported during a late-breaking abstract session at the annual meeting of the American Society of Hematology.

Overall survival was not reached in either group, but was also significantly longer with idelalisib (HR, 0.28; P = .018).

New therapies are needed for relapsed chronic lymphocytic leukemia patients (CLL), especially those who are unfit for chemoimmunotherapy, observed Dr. Furman, head of the CLL and Waldenström’s macroglobulinemia program at Cornell University, New York

Relapsed CLL responds poorly to available therapies, and older patients and those with comorbidities or poor renal/bone marrow function often cannot tolerate standard chemoimmunotherapy.

A new drug application for refractory indolent non-Hodgkin lymphoma was submitted in September for idelalisib and the oral phosphoinositide 3-kinase–delta inhibitor was subsequently granted breakthrough therapy status for relapsed CLL based on the Study 116 findings.

The positive findings also prompted the phase III trial to be halted early in November.

Idelalisib had an acceptable safety profile, with adverse events leading 9 patients to stop idelalisib combination therapy vs. 11 controls, Dr. Furman said.

Infusion-related reactions were also lower, possibly because idelalisib had an impact on the tolerability of rituximab, he said. No patient on idelalisib had a grade 3 or higher infusion reaction vs. four on rituximab alone.

As seen in another idelalisib trial reported at the meeting, grade 3/4 transaminase elevations were more common with the addition of idelalisib to rituximab (six patients vs. one patient). Four of the six idelalisib patients with this event were successfully rechallenged, he said.

Concerns were raised by the audience, however, about whether single-agent rituximab was an appropriate comparator since 88% of controls had already been treated with rituximab.

In response to the criticism, Dr. Furman reminded the audience that all patients were unfit for chemotherapy and that physicians had to be comfortable with the protocol in order to enroll patients.

"You have to remember rituximab is actually, in practice, the most commonly used agent for these patients and by giving sort of a stepped-up dosing, they’d hopefully be getting sufficient therapy to better the patients’ outcome," he added.

Commenting on the results, Dr. Wendy Stock of the University of Chicago, who was a session co-moderator, said the choice of the control arm was her one concern, but that the study design would likely have not been improved if the previous standard, chlorambucil chemotherapy, had been used as the control.

"I think the data are very compelling in terms of the efficacy of this new agent, and we’ll have to see now how it gets incorporated with other novel agents and/or moved into the United States and Europe evenly randomized 220 patients to eight infusions of rituximab over 24 weeks plus either idelalisib 150 mg or placebo twice daily until disease progression. Rituximab was dosed at 375 mg/m² in week 1, 500 mg/m² every 2 weeks for four doses, followed by 500 mg/m² every 4 weeks for three more doses.

Patients had received a median of three prior therapies, a median Cumulative Illness Rating Scale score of 8, and a median age of 71 years.

The addition of idelalisib to rituximab increased the overall response rate from 13% to 81% (P less than .0001) and the number of patients achieving at least a 50% reduction in lymph nodes from 4% to 93% (P less than .0001), Dr. Furman said.

Idelalisib is currently being evaluated in more than a dozen studies including a phase II study of combination therapy with the experimental spleen tyrosine kinase inhibitor GS-9973 in a variety of relapsed or refractory hematologic malignancies.

Dr. Furman reported research funding from and board of directors or advisory committee membership with Gilead Sciences, which is developing idelalisib.

[email protected]

NEW ORLEANS – Adding idelalisib to rituximab significantly extends survival in patients with heavily pretreated relapsed chronic lymphocytic leukemia unsuitable for chemotherapy, according to results from Study 116.

The primary endpoint of median progression-free survival (PFS) was 5.5 months with rituximab (Rituxan) plus placebo and had not been reached with rituximab plus idelalisib (hazard ratio, 0.15; P less than .0001).

The PFS advantage was seen across all subgroups including patients with the 17p deletion and TP53 mutations, Dr. Richard R. Furman reported during a late-breaking abstract session at the annual meeting of the American Society of Hematology.

Overall survival was not reached in either group, but was also significantly longer with idelalisib (HR, 0.28; P = .018).

New therapies are needed for relapsed chronic lymphocytic leukemia patients (CLL), especially those who are unfit for chemoimmunotherapy, observed Dr. Furman, head of the CLL and Waldenström’s macroglobulinemia program at Cornell University, New York

Relapsed CLL responds poorly to available therapies, and older patients and those with comorbidities or poor renal/bone marrow function often cannot tolerate standard chemoimmunotherapy.

A new drug application for refractory indolent non-Hodgkin lymphoma was submitted in September for idelalisib and the oral phosphoinositide 3-kinase–delta inhibitor was subsequently granted breakthrough therapy status for relapsed CLL based on the Study 116 findings.

The positive findings also prompted the phase III trial to be halted early in November.

Idelalisib had an acceptable safety profile, with adverse events leading 9 patients to stop idelalisib combination therapy vs. 11 controls, Dr. Furman said.

Infusion-related reactions were also lower, possibly because idelalisib had an impact on the tolerability of rituximab, he said. No patient on idelalisib had a grade 3 or higher infusion reaction vs. four on rituximab alone.

As seen in another idelalisib trial reported at the meeting, grade 3/4 transaminase elevations were more common with the addition of idelalisib to rituximab (six patients vs. one patient). Four of the six idelalisib patients with this event were successfully rechallenged, he said.

Concerns were raised by the audience, however, about whether single-agent rituximab was an appropriate comparator since 88% of controls had already been treated with rituximab.

In response to the criticism, Dr. Furman reminded the audience that all patients were unfit for chemotherapy and that physicians had to be comfortable with the protocol in order to enroll patients.

"You have to remember rituximab is actually, in practice, the most commonly used agent for these patients and by giving sort of a stepped-up dosing, they’d hopefully be getting sufficient therapy to better the patients’ outcome," he added.

Commenting on the results, Dr. Wendy Stock of the University of Chicago, who was a session co-moderator, said the choice of the control arm was her one concern, but that the study design would likely have not been improved if the previous standard, chlorambucil chemotherapy, had been used as the control.

"I think the data are very compelling in terms of the efficacy of this new agent, and we’ll have to see now how it gets incorporated with other novel agents and/or moved into the United States and Europe evenly randomized 220 patients to eight infusions of rituximab over 24 weeks plus either idelalisib 150 mg or placebo twice daily until disease progression. Rituximab was dosed at 375 mg/m² in week 1, 500 mg/m² every 2 weeks for four doses, followed by 500 mg/m² every 4 weeks for three more doses.

Patients had received a median of three prior therapies, a median Cumulative Illness Rating Scale score of 8, and a median age of 71 years.

The addition of idelalisib to rituximab increased the overall response rate from 13% to 81% (P less than .0001) and the number of patients achieving at least a 50% reduction in lymph nodes from 4% to 93% (P less than .0001), Dr. Furman said.

Idelalisib is currently being evaluated in more than a dozen studies including a phase II study of combination therapy with the experimental spleen tyrosine kinase inhibitor GS-9973 in a variety of relapsed or refractory hematologic malignancies.

Dr. Furman reported research funding from and board of directors or advisory committee membership with Gilead Sciences, which is developing idelalisib.

[email protected]

NEW ORLEANS – Adding idelalisib to rituximab significantly extends survival in patients with heavily pretreated relapsed chronic lymphocytic leukemia unsuitable for chemotherapy, according to results from Study 116.

The primary endpoint of median progression-free survival (PFS) was 5.5 months with rituximab (Rituxan) plus placebo and had not been reached with rituximab plus idelalisib (hazard ratio, 0.15; P less than .0001).

The PFS advantage was seen across all subgroups including patients with the 17p deletion and TP53 mutations, Dr. Richard R. Furman reported during a late-breaking abstract session at the annual meeting of the American Society of Hematology.

Overall survival was not reached in either group, but was also significantly longer with idelalisib (HR, 0.28; P = .018).

New therapies are needed for relapsed chronic lymphocytic leukemia patients (CLL), especially those who are unfit for chemoimmunotherapy, observed Dr. Furman, head of the CLL and Waldenström’s macroglobulinemia program at Cornell University, New York

Relapsed CLL responds poorly to available therapies, and older patients and those with comorbidities or poor renal/bone marrow function often cannot tolerate standard chemoimmunotherapy.

A new drug application for refractory indolent non-Hodgkin lymphoma was submitted in September for idelalisib and the oral phosphoinositide 3-kinase–delta inhibitor was subsequently granted breakthrough therapy status for relapsed CLL based on the Study 116 findings.

The positive findings also prompted the phase III trial to be halted early in November.

Idelalisib had an acceptable safety profile, with adverse events leading 9 patients to stop idelalisib combination therapy vs. 11 controls, Dr. Furman said.

Infusion-related reactions were also lower, possibly because idelalisib had an impact on the tolerability of rituximab, he said. No patient on idelalisib had a grade 3 or higher infusion reaction vs. four on rituximab alone.

As seen in another idelalisib trial reported at the meeting, grade 3/4 transaminase elevations were more common with the addition of idelalisib to rituximab (six patients vs. one patient). Four of the six idelalisib patients with this event were successfully rechallenged, he said.

Concerns were raised by the audience, however, about whether single-agent rituximab was an appropriate comparator since 88% of controls had already been treated with rituximab.

In response to the criticism, Dr. Furman reminded the audience that all patients were unfit for chemotherapy and that physicians had to be comfortable with the protocol in order to enroll patients.

"You have to remember rituximab is actually, in practice, the most commonly used agent for these patients and by giving sort of a stepped-up dosing, they’d hopefully be getting sufficient therapy to better the patients’ outcome," he added.

Commenting on the results, Dr. Wendy Stock of the University of Chicago, who was a session co-moderator, said the choice of the control arm was her one concern, but that the study design would likely have not been improved if the previous standard, chlorambucil chemotherapy, had been used as the control.

"I think the data are very compelling in terms of the efficacy of this new agent, and we’ll have to see now how it gets incorporated with other novel agents and/or moved into the United States and Europe evenly randomized 220 patients to eight infusions of rituximab over 24 weeks plus either idelalisib 150 mg or placebo twice daily until disease progression. Rituximab was dosed at 375 mg/m² in week 1, 500 mg/m² every 2 weeks for four doses, followed by 500 mg/m² every 4 weeks for three more doses.

Patients had received a median of three prior therapies, a median Cumulative Illness Rating Scale score of 8, and a median age of 71 years.

The addition of idelalisib to rituximab increased the overall response rate from 13% to 81% (P less than .0001) and the number of patients achieving at least a 50% reduction in lymph nodes from 4% to 93% (P less than .0001), Dr. Furman said.

Idelalisib is currently being evaluated in more than a dozen studies including a phase II study of combination therapy with the experimental spleen tyrosine kinase inhibitor GS-9973 in a variety of relapsed or refractory hematologic malignancies.

Dr. Furman reported research funding from and board of directors or advisory committee membership with Gilead Sciences, which is developing idelalisib.

[email protected]