IMPORTANCE OF PHARMACIST CONSULTATION TO PREDICT EARLY TOXICITIES WITH IBRUTINIB AND IDELALISIB: A SURVEY FROM 119 PATIENTS TREATED IN A SINGLE INSTITUTION
(Abstract release date: 05/19/16)
EHA Library. Ysebaert L. 06/09/16; 132627; E1078
Prof. Loïc Ysebaert
Contributions
Contributions
Abstract
Abstract: E1078
Type: Eposter Presentation
Background
Ibrutinib (IB) and idelalisib (ID) have changed treatment paradigms in the management of R/R B-cell malignancies but their safety profile in the real-world setting is ill-defined.
Aims
Here, we report on the impact of drug-drug interactions (DDI) on early toxicity in a series of 119 patients (28 prospectively, 91 retrospectively evaluated) with CLL, mantle cell (MCL) and follicular lymphoma (FL), treated outside the context of clinical trials.
Methods
Consecutive IB/ID pts who initiated therapy off-protocol at Institut Universitaire du Cancer (IUC) Toulouse-Oncopole from Apr2014 to Dec2015 were included (given they had been exposed to drug at least 1mo). A medication review for potential DDI was performed by a clinical pharmacist on all files. Baseline characteristics, concomitant medications (COMED), and toxicities were recorded. Toxicity at month 1 (TOXM1) was defined by any grade 3-4, or grade 2 but leading to dose reductions due to impact on quality of life (always on patients' demand).
Results
67 IB pts (52 CLL, 12 MCL) and 52 ID pts (39 CLL, 13 FL) were assessed (all with a median of 3 previous lines of therapy).Ibrutinib: median age was 68.6y, with a median number of 3.6 COMED (range 0-14, 30% with COMED>5, defining polypharmacy). Fifty-five % were taking substrates of CYP3A4/Pgp, 21% inhibitors of Pgp, 16% and 25% inhibitors of CYP2D6 and 3A4, respectively. No dose reduction was allowed at the initiation of therapy. TOXM1 was reported in 22/67 pts (32.8%), with only 5/22 grade 3-4 toxicities, and 17/22 grade 2 impacting QoL (mostly cramps, diarrhea, dyspepsia, rash). TOXM1 was not correlated to type of lymphoma, previous therapies, gender, age, COMED>5, but correlated statistically to Pgp inhibitors (52.4% vs 23.9%, p=0.02) or CYP3A4 inhibitors (57% vs 26.4%, p=0.03) concomitant drug intake, as could be expected from pharmacokinetics profile of ibrutinib. PFS was not impacted by dose reduction.Idelalisib: median age was 74y, with a median number of 4.2 COMED (range 0-12, 41% with COMED>5). Sixty-five % were taking substrates of CYP3A4/Pgp, 36% inhibitors of Pgp, 0% and 25% inhibitors of CYP2D6 and 3A4, respectively. TOXM1 was reported in 15/52 pts (28.8%), but due exclusively to grade 3-4 events: neutropenia (23%), mucositis (4%), diarrhea/transaminitis (2% each). TOXM1 was not correlated to type of lymphoma, age, number or type of COMED, but to female gender (50% vs 14%, p=0.01). Aldehyde oxydase activity (the main pathway of ID metabolism) is poorly defined in humans, but reduced in female rats. When looking at the first 3 mo of ID therapy, women had an increased frequency of neutropenic (39% vs 14.44%) and diarrhea (16.7% vs 2.9%) events of any grade, but less transaminitis events(5.5% vs 9%), as compared to men. TOXM1 led to dose reductions after a month of ID in 44.5% and 11.2% of female/male pts, respectively (impacting PFS). At 6mo follow-up, 38.5% of patients were still on therapy (most discontinuations due to grade 3-4 AE).
Conclusion
DDI were found to impact early toxicities with IB but not with ID, emphasizing the urgent need of better PK/toxicity evaluation for both drugs in real-life practice. Such prospective evaluation is just starting in our institution (protocol PK-E3i) to better monitor plasma levels (and adequately adapt drug dosage), and better support patients' compliance in the long-term.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Drug interaction
Type: Eposter Presentation
Background
Ibrutinib (IB) and idelalisib (ID) have changed treatment paradigms in the management of R/R B-cell malignancies but their safety profile in the real-world setting is ill-defined.
Aims
Here, we report on the impact of drug-drug interactions (DDI) on early toxicity in a series of 119 patients (28 prospectively, 91 retrospectively evaluated) with CLL, mantle cell (MCL) and follicular lymphoma (FL), treated outside the context of clinical trials.
Methods
Consecutive IB/ID pts who initiated therapy off-protocol at Institut Universitaire du Cancer (IUC) Toulouse-Oncopole from Apr2014 to Dec2015 were included (given they had been exposed to drug at least 1mo). A medication review for potential DDI was performed by a clinical pharmacist on all files. Baseline characteristics, concomitant medications (COMED), and toxicities were recorded. Toxicity at month 1 (TOXM1) was defined by any grade 3-4, or grade 2 but leading to dose reductions due to impact on quality of life (always on patients' demand).
Results
67 IB pts (52 CLL, 12 MCL) and 52 ID pts (39 CLL, 13 FL) were assessed (all with a median of 3 previous lines of therapy).Ibrutinib: median age was 68.6y, with a median number of 3.6 COMED (range 0-14, 30% with COMED>5, defining polypharmacy). Fifty-five % were taking substrates of CYP3A4/Pgp, 21% inhibitors of Pgp, 16% and 25% inhibitors of CYP2D6 and 3A4, respectively. No dose reduction was allowed at the initiation of therapy. TOXM1 was reported in 22/67 pts (32.8%), with only 5/22 grade 3-4 toxicities, and 17/22 grade 2 impacting QoL (mostly cramps, diarrhea, dyspepsia, rash). TOXM1 was not correlated to type of lymphoma, previous therapies, gender, age, COMED>5, but correlated statistically to Pgp inhibitors (52.4% vs 23.9%, p=0.02) or CYP3A4 inhibitors (57% vs 26.4%, p=0.03) concomitant drug intake, as could be expected from pharmacokinetics profile of ibrutinib. PFS was not impacted by dose reduction.Idelalisib: median age was 74y, with a median number of 4.2 COMED (range 0-12, 41% with COMED>5). Sixty-five % were taking substrates of CYP3A4/Pgp, 36% inhibitors of Pgp, 0% and 25% inhibitors of CYP2D6 and 3A4, respectively. TOXM1 was reported in 15/52 pts (28.8%), but due exclusively to grade 3-4 events: neutropenia (23%), mucositis (4%), diarrhea/transaminitis (2% each). TOXM1 was not correlated to type of lymphoma, age, number or type of COMED, but to female gender (50% vs 14%, p=0.01). Aldehyde oxydase activity (the main pathway of ID metabolism) is poorly defined in humans, but reduced in female rats. When looking at the first 3 mo of ID therapy, women had an increased frequency of neutropenic (39% vs 14.44%) and diarrhea (16.7% vs 2.9%) events of any grade, but less transaminitis events(5.5% vs 9%), as compared to men. TOXM1 led to dose reductions after a month of ID in 44.5% and 11.2% of female/male pts, respectively (impacting PFS). At 6mo follow-up, 38.5% of patients were still on therapy (most discontinuations due to grade 3-4 AE).
Conclusion
DDI were found to impact early toxicities with IB but not with ID, emphasizing the urgent need of better PK/toxicity evaluation for both drugs in real-life practice. Such prospective evaluation is just starting in our institution (protocol PK-E3i) to better monitor plasma levels (and adequately adapt drug dosage), and better support patients' compliance in the long-term.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Drug interaction
Abstract: E1078
Type: Eposter Presentation
Background
Ibrutinib (IB) and idelalisib (ID) have changed treatment paradigms in the management of R/R B-cell malignancies but their safety profile in the real-world setting is ill-defined.
Aims
Here, we report on the impact of drug-drug interactions (DDI) on early toxicity in a series of 119 patients (28 prospectively, 91 retrospectively evaluated) with CLL, mantle cell (MCL) and follicular lymphoma (FL), treated outside the context of clinical trials.
Methods
Consecutive IB/ID pts who initiated therapy off-protocol at Institut Universitaire du Cancer (IUC) Toulouse-Oncopole from Apr2014 to Dec2015 were included (given they had been exposed to drug at least 1mo). A medication review for potential DDI was performed by a clinical pharmacist on all files. Baseline characteristics, concomitant medications (COMED), and toxicities were recorded. Toxicity at month 1 (TOXM1) was defined by any grade 3-4, or grade 2 but leading to dose reductions due to impact on quality of life (always on patients' demand).
Results
67 IB pts (52 CLL, 12 MCL) and 52 ID pts (39 CLL, 13 FL) were assessed (all with a median of 3 previous lines of therapy).Ibrutinib: median age was 68.6y, with a median number of 3.6 COMED (range 0-14, 30% with COMED>5, defining polypharmacy). Fifty-five % were taking substrates of CYP3A4/Pgp, 21% inhibitors of Pgp, 16% and 25% inhibitors of CYP2D6 and 3A4, respectively. No dose reduction was allowed at the initiation of therapy. TOXM1 was reported in 22/67 pts (32.8%), with only 5/22 grade 3-4 toxicities, and 17/22 grade 2 impacting QoL (mostly cramps, diarrhea, dyspepsia, rash). TOXM1 was not correlated to type of lymphoma, previous therapies, gender, age, COMED>5, but correlated statistically to Pgp inhibitors (52.4% vs 23.9%, p=0.02) or CYP3A4 inhibitors (57% vs 26.4%, p=0.03) concomitant drug intake, as could be expected from pharmacokinetics profile of ibrutinib. PFS was not impacted by dose reduction.Idelalisib: median age was 74y, with a median number of 4.2 COMED (range 0-12, 41% with COMED>5). Sixty-five % were taking substrates of CYP3A4/Pgp, 36% inhibitors of Pgp, 0% and 25% inhibitors of CYP2D6 and 3A4, respectively. TOXM1 was reported in 15/52 pts (28.8%), but due exclusively to grade 3-4 events: neutropenia (23%), mucositis (4%), diarrhea/transaminitis (2% each). TOXM1 was not correlated to type of lymphoma, age, number or type of COMED, but to female gender (50% vs 14%, p=0.01). Aldehyde oxydase activity (the main pathway of ID metabolism) is poorly defined in humans, but reduced in female rats. When looking at the first 3 mo of ID therapy, women had an increased frequency of neutropenic (39% vs 14.44%) and diarrhea (16.7% vs 2.9%) events of any grade, but less transaminitis events(5.5% vs 9%), as compared to men. TOXM1 led to dose reductions after a month of ID in 44.5% and 11.2% of female/male pts, respectively (impacting PFS). At 6mo follow-up, 38.5% of patients were still on therapy (most discontinuations due to grade 3-4 AE).
Conclusion
DDI were found to impact early toxicities with IB but not with ID, emphasizing the urgent need of better PK/toxicity evaluation for both drugs in real-life practice. Such prospective evaluation is just starting in our institution (protocol PK-E3i) to better monitor plasma levels (and adequately adapt drug dosage), and better support patients' compliance in the long-term.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Drug interaction
Type: Eposter Presentation
Background
Ibrutinib (IB) and idelalisib (ID) have changed treatment paradigms in the management of R/R B-cell malignancies but their safety profile in the real-world setting is ill-defined.
Aims
Here, we report on the impact of drug-drug interactions (DDI) on early toxicity in a series of 119 patients (28 prospectively, 91 retrospectively evaluated) with CLL, mantle cell (MCL) and follicular lymphoma (FL), treated outside the context of clinical trials.
Methods
Consecutive IB/ID pts who initiated therapy off-protocol at Institut Universitaire du Cancer (IUC) Toulouse-Oncopole from Apr2014 to Dec2015 were included (given they had been exposed to drug at least 1mo). A medication review for potential DDI was performed by a clinical pharmacist on all files. Baseline characteristics, concomitant medications (COMED), and toxicities were recorded. Toxicity at month 1 (TOXM1) was defined by any grade 3-4, or grade 2 but leading to dose reductions due to impact on quality of life (always on patients' demand).
Results
67 IB pts (52 CLL, 12 MCL) and 52 ID pts (39 CLL, 13 FL) were assessed (all with a median of 3 previous lines of therapy).Ibrutinib: median age was 68.6y, with a median number of 3.6 COMED (range 0-14, 30% with COMED>5, defining polypharmacy). Fifty-five % were taking substrates of CYP3A4/Pgp, 21% inhibitors of Pgp, 16% and 25% inhibitors of CYP2D6 and 3A4, respectively. No dose reduction was allowed at the initiation of therapy. TOXM1 was reported in 22/67 pts (32.8%), with only 5/22 grade 3-4 toxicities, and 17/22 grade 2 impacting QoL (mostly cramps, diarrhea, dyspepsia, rash). TOXM1 was not correlated to type of lymphoma, previous therapies, gender, age, COMED>5, but correlated statistically to Pgp inhibitors (52.4% vs 23.9%, p=0.02) or CYP3A4 inhibitors (57% vs 26.4%, p=0.03) concomitant drug intake, as could be expected from pharmacokinetics profile of ibrutinib. PFS was not impacted by dose reduction.Idelalisib: median age was 74y, with a median number of 4.2 COMED (range 0-12, 41% with COMED>5). Sixty-five % were taking substrates of CYP3A4/Pgp, 36% inhibitors of Pgp, 0% and 25% inhibitors of CYP2D6 and 3A4, respectively. TOXM1 was reported in 15/52 pts (28.8%), but due exclusively to grade 3-4 events: neutropenia (23%), mucositis (4%), diarrhea/transaminitis (2% each). TOXM1 was not correlated to type of lymphoma, age, number or type of COMED, but to female gender (50% vs 14%, p=0.01). Aldehyde oxydase activity (the main pathway of ID metabolism) is poorly defined in humans, but reduced in female rats. When looking at the first 3 mo of ID therapy, women had an increased frequency of neutropenic (39% vs 14.44%) and diarrhea (16.7% vs 2.9%) events of any grade, but less transaminitis events(5.5% vs 9%), as compared to men. TOXM1 led to dose reductions after a month of ID in 44.5% and 11.2% of female/male pts, respectively (impacting PFS). At 6mo follow-up, 38.5% of patients were still on therapy (most discontinuations due to grade 3-4 AE).
Conclusion
DDI were found to impact early toxicities with IB but not with ID, emphasizing the urgent need of better PK/toxicity evaluation for both drugs in real-life practice. Such prospective evaluation is just starting in our institution (protocol PK-E3i) to better monitor plasma levels (and adequately adapt drug dosage), and better support patients' compliance in the long-term.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Drug interaction
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