Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: At 2 years, molecular recurrence-free survival (MRFS) after imatinib discontinuation was observed in over half of the patients with chronic phase-chronic myeloid leukemia (CML-CP) with sustained molecular response of 4log (MR4). MR of 4.5log (MR4.5) was associated with a lower risk of relapse.

Major finding: At 24 months, MRFS was 54% (95% CI, 39%-75%). Molecular relapse was observed in 42% of patients. All patients reachieved major molecular response after resuming imatinib. MR4.5 at discontinuation was associated with a lower risk of molecular relapse (odds ratio, 0.32; P = .03).

Study details: Findings are from a prospective study that evaluated treatment-free survival after imatinib discontinuation in 31 patients with CML-CP with sustained MR4 for at least 12 months and treated with first-line imatinib for at least 36 months.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

Source: Seguro FS et al. Leuk Res. 2021 Jan 21. doi: 10.1016/j.leukres.2021.106516.

Key clinical point: At 2 years, molecular recurrence-free survival (MRFS) after imatinib discontinuation was observed in over half of the patients with chronic phase-chronic myeloid leukemia (CML-CP) with sustained molecular response of 4log (MR4). MR of 4.5log (MR4.5) was associated with a lower risk of relapse.

Major finding: At 24 months, MRFS was 54% (95% CI, 39%-75%). Molecular relapse was observed in 42% of patients. All patients reachieved major molecular response after resuming imatinib. MR4.5 at discontinuation was associated with a lower risk of molecular relapse (odds ratio, 0.32; P = .03).

Study details: Findings are from a prospective study that evaluated treatment-free survival after imatinib discontinuation in 31 patients with CML-CP with sustained MR4 for at least 12 months and treated with first-line imatinib for at least 36 months.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

Source: Seguro FS et al. Leuk Res. 2021 Jan 21. doi: 10.1016/j.leukres.2021.106516.

Key clinical point: At 2 years, molecular recurrence-free survival (MRFS) after imatinib discontinuation was observed in over half of the patients with chronic phase-chronic myeloid leukemia (CML-CP) with sustained molecular response of 4log (MR4). MR of 4.5log (MR4.5) was associated with a lower risk of relapse.

Major finding: At 24 months, MRFS was 54% (95% CI, 39%-75%). Molecular relapse was observed in 42% of patients. All patients reachieved major molecular response after resuming imatinib. MR4.5 at discontinuation was associated with a lower risk of molecular relapse (odds ratio, 0.32; P = .03).

Study details: Findings are from a prospective study that evaluated treatment-free survival after imatinib discontinuation in 31 patients with CML-CP with sustained MR4 for at least 12 months and treated with first-line imatinib for at least 36 months.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

Source: Seguro FS et al. Leuk Res. 2021 Jan 21. doi: 10.1016/j.leukres.2021.106516.

Key clinical point: Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) with a higher dasatinib dose adjusted for body weight (dose/BW) experienced a higher risk of dose-limiting toxicities (DLTs). The fixed starting dose of dasatinib 100 mg may not be optimal in Asian patients.

Major finding: By 36 months after initiation of dasatinib 100 mg once daily (OD) as frontline therapy, 55.9% of patients experienced at least 1 DLT. Higher dasatinib dose/BW was associated with a higher risk of DLT occurrence (odds ratio, 4.84; P = .03).

Study details: This study assessed the effect of a fixed starting dose of dasatinib (100 mg OD) in 102 Asian patients with newly diagnosed CML-CP.

Disclosures: This study was funded by the National Research Foundation of Korea, the Foundation of Pharmacy Education and Research, and the Research Institutes of Pharmaceutical Sciences (Seoul National University). The lead author had no disclosures. DW Kim reported the use of clinical data collected from a separate research study (funded by Bristol-Myers Squibb) for this study.

Source: Shin H et al. Clin Lymphoma Myeloma Leuk. 2021 Feb 1 doi: 10.1016/j.clml.2021.01.020.

Key clinical point: Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) with a higher dasatinib dose adjusted for body weight (dose/BW) experienced a higher risk of dose-limiting toxicities (DLTs). The fixed starting dose of dasatinib 100 mg may not be optimal in Asian patients.

Major finding: By 36 months after initiation of dasatinib 100 mg once daily (OD) as frontline therapy, 55.9% of patients experienced at least 1 DLT. Higher dasatinib dose/BW was associated with a higher risk of DLT occurrence (odds ratio, 4.84; P = .03).

Study details: This study assessed the effect of a fixed starting dose of dasatinib (100 mg OD) in 102 Asian patients with newly diagnosed CML-CP.

Disclosures: This study was funded by the National Research Foundation of Korea, the Foundation of Pharmacy Education and Research, and the Research Institutes of Pharmaceutical Sciences (Seoul National University). The lead author had no disclosures. DW Kim reported the use of clinical data collected from a separate research study (funded by Bristol-Myers Squibb) for this study.

Source: Shin H et al. Clin Lymphoma Myeloma Leuk. 2021 Feb 1 doi: 10.1016/j.clml.2021.01.020.

Key clinical point: Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) with a higher dasatinib dose adjusted for body weight (dose/BW) experienced a higher risk of dose-limiting toxicities (DLTs). The fixed starting dose of dasatinib 100 mg may not be optimal in Asian patients.

Major finding: By 36 months after initiation of dasatinib 100 mg once daily (OD) as frontline therapy, 55.9% of patients experienced at least 1 DLT. Higher dasatinib dose/BW was associated with a higher risk of DLT occurrence (odds ratio, 4.84; P = .03).

Study details: This study assessed the effect of a fixed starting dose of dasatinib (100 mg OD) in 102 Asian patients with newly diagnosed CML-CP.

Disclosures: This study was funded by the National Research Foundation of Korea, the Foundation of Pharmacy Education and Research, and the Research Institutes of Pharmaceutical Sciences (Seoul National University). The lead author had no disclosures. DW Kim reported the use of clinical data collected from a separate research study (funded by Bristol-Myers Squibb) for this study.

Source: Shin H et al. Clin Lymphoma Myeloma Leuk. 2021 Feb 1 doi: 10.1016/j.clml.2021.01.020.

Key clinical point: Late relapses do occur after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) at 36 months, with molecular response (MR) status at 36 months being highly predictive of subsequent molecular relapse.

Major finding: During a follow-up of 72 months, 10.8% of patients in TFR at 36 months lost major MR. Not being in MR4 at 36 months of TKI discontinuation was associated with an 85% higher risk of molecular relapse during the subsequent 3 years.

Study details: Findings are from the 6-year follow-up (AFTER-SKI) of 111 patients with CML-CP who were in TFR at 36 months after TKI discontinuation from the EURO-SKI trial.

Disclosures: This study was funded by Lund University and Skane University Hospital. U Olsson-Strömberg, P Koskenvesa, and D Žáčková reported consulting for, being on speaker’s and advisory boards, or receiving honoraria from various pharmaceutical companies. The remaining authors had no disclosures.

Source: Richter J et al. Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01173-w.

Key clinical point: Late relapses do occur after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) at 36 months, with molecular response (MR) status at 36 months being highly predictive of subsequent molecular relapse.

Major finding: During a follow-up of 72 months, 10.8% of patients in TFR at 36 months lost major MR. Not being in MR4 at 36 months of TKI discontinuation was associated with an 85% higher risk of molecular relapse during the subsequent 3 years.

Study details: Findings are from the 6-year follow-up (AFTER-SKI) of 111 patients with CML-CP who were in TFR at 36 months after TKI discontinuation from the EURO-SKI trial.

Disclosures: This study was funded by Lund University and Skane University Hospital. U Olsson-Strömberg, P Koskenvesa, and D Žáčková reported consulting for, being on speaker’s and advisory boards, or receiving honoraria from various pharmaceutical companies. The remaining authors had no disclosures.

Source: Richter J et al. Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01173-w.

Key clinical point: Late relapses do occur after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) at 36 months, with molecular response (MR) status at 36 months being highly predictive of subsequent molecular relapse.

Major finding: During a follow-up of 72 months, 10.8% of patients in TFR at 36 months lost major MR. Not being in MR4 at 36 months of TKI discontinuation was associated with an 85% higher risk of molecular relapse during the subsequent 3 years.

Study details: Findings are from the 6-year follow-up (AFTER-SKI) of 111 patients with CML-CP who were in TFR at 36 months after TKI discontinuation from the EURO-SKI trial.

Disclosures: This study was funded by Lund University and Skane University Hospital. U Olsson-Strömberg, P Koskenvesa, and D Žáčková reported consulting for, being on speaker’s and advisory boards, or receiving honoraria from various pharmaceutical companies. The remaining authors had no disclosures.

Source: Richter J et al. Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01173-w.

Key clinical point: Combination of imatinib (IM) with cytarabine (AraC) or pegylated interferon alpha2a (PegIFN-α2a) or a higher IM dose (600 mg; IM-600) did not improve long-term survival vs. IM 400 mg (IM-400) in patients with chronic myeloid leukemia in the chronic phase (CML-CP).

Major finding: At 15 years, overall survival was similar across IM-400 (85%; 95% confidence interval [CI], 78%-90%), IM-600 (83%; 95% CI, 75%-88%), IM-400+AraC (80%; 95% CI, 73%-85%), and IM-400+PegIFN-α2a (82%; 95% CI, 75%-87%) arms. Progression-free survival was also similar between arms.

Study details: Findings are from French SPIRIT phase 3 trial including 787 patients with CML-CP randomly allocated to frontline treatment with IM-400 (n=223), IM-600 (n=171), IM-400+AraC (n=172), and IM-400+PegIFN-α2a (n=221).

Disclosures: The trial was supported by grants from the French Minister of Health, Novartis, and Roche Pharma. The lead author reported ties with Novartis, Roche, BMS, and Celgene. Some of the other authors also declared receiving honoraria and/or research support from various pharmaceutical companies.

Source: Guilhot F et al. Leukemia. 2021 Jan 22. doi: 10.1038/s41375-020-01117-w.

Key clinical point: Combination of imatinib (IM) with cytarabine (AraC) or pegylated interferon alpha2a (PegIFN-α2a) or a higher IM dose (600 mg; IM-600) did not improve long-term survival vs. IM 400 mg (IM-400) in patients with chronic myeloid leukemia in the chronic phase (CML-CP).

Major finding: At 15 years, overall survival was similar across IM-400 (85%; 95% confidence interval [CI], 78%-90%), IM-600 (83%; 95% CI, 75%-88%), IM-400+AraC (80%; 95% CI, 73%-85%), and IM-400+PegIFN-α2a (82%; 95% CI, 75%-87%) arms. Progression-free survival was also similar between arms.

Study details: Findings are from French SPIRIT phase 3 trial including 787 patients with CML-CP randomly allocated to frontline treatment with IM-400 (n=223), IM-600 (n=171), IM-400+AraC (n=172), and IM-400+PegIFN-α2a (n=221).

Disclosures: The trial was supported by grants from the French Minister of Health, Novartis, and Roche Pharma. The lead author reported ties with Novartis, Roche, BMS, and Celgene. Some of the other authors also declared receiving honoraria and/or research support from various pharmaceutical companies.

Source: Guilhot F et al. Leukemia. 2021 Jan 22. doi: 10.1038/s41375-020-01117-w.

Key clinical point: Combination of imatinib (IM) with cytarabine (AraC) or pegylated interferon alpha2a (PegIFN-α2a) or a higher IM dose (600 mg; IM-600) did not improve long-term survival vs. IM 400 mg (IM-400) in patients with chronic myeloid leukemia in the chronic phase (CML-CP).

Major finding: At 15 years, overall survival was similar across IM-400 (85%; 95% confidence interval [CI], 78%-90%), IM-600 (83%; 95% CI, 75%-88%), IM-400+AraC (80%; 95% CI, 73%-85%), and IM-400+PegIFN-α2a (82%; 95% CI, 75%-87%) arms. Progression-free survival was also similar between arms.

Study details: Findings are from French SPIRIT phase 3 trial including 787 patients with CML-CP randomly allocated to frontline treatment with IM-400 (n=223), IM-600 (n=171), IM-400+AraC (n=172), and IM-400+PegIFN-α2a (n=221).

Disclosures: The trial was supported by grants from the French Minister of Health, Novartis, and Roche Pharma. The lead author reported ties with Novartis, Roche, BMS, and Celgene. Some of the other authors also declared receiving honoraria and/or research support from various pharmaceutical companies.

Source: Guilhot F et al. Leukemia. 2021 Jan 22. doi: 10.1038/s41375-020-01117-w.

Most checkpoint inhibitor–induced rheumatic complications in cancer patients can be treated successfully with corticosteroids, albeit often at considerably higher doses than rheumatologists typically use in managing rheumatoid arthritis, Eric M. Ruderman, MD, observed at the 2021 Rheumatology Winter Clinical Symposium.

“In RA, we’re all used to the idea that 5 or 10 mg of corticosteroids per day can make a tremendous difference. That’s not always the case here. Patients who develop rheumatic immunotherapy-related adverse events often require 20-30 mg/day to get symptoms under control,” according to Dr. Ruderman, professor of medicine (rheumatology) at Northwestern University, Chicago.

This may be in part because oncologists typically don’t refer affected patients to rheumatologists early on. Guidelines from the National Comprehensive Cancer Network and other oncology groups suggest referral only once a patient develops grade 3 immunotherapy-related rheumatic adverse events, meaning the symptoms significantly impair daily activities, he explained.

Checkpoint inhibitors, which induce T-cell activation to fight the patient’s malignancy, can produce a plethora of off-target effects. These adverse events may involve the skin, heart, lungs, kidneys, eyes, blood, GI tract, and endocrine organs. The drugs also can cause rheumatic or neurologic complications. The most common of these adverse events are colitis and rash. Next most common are arthritis and arthralgia. Rheumatic side effects are most common as a consequence of immunotherapy using a CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, but can also occur in association with programmed cell death protein 1 (PD-1) inhibitors and PD-ligand 1 inhibitors. Arthritis and other rheumatic adverse events are more common in patients undergoing combination therapy.

Some form of frank inflammatory arthritis occurs in 5%-10% of cancer patients undergoing checkpoint inhibitor therapy. This can manifest as an RA-like polyarthritis, spondyloarthritis, polymyalgia rheumatica, necrotizing myositis, or vasculitis. Arthralgia occurs in up to 40% of treated patients.

This immunotherapy-related arthritis is typically more inflammatory than RA. It also has a much more abrupt onset. It is usually seronegative and has no gender predisposition, and the limited available evidence to date suggests there is no increased risk of this complication in checkpoint inhibitor–treated patients with a history of prior rheumatic disease, according to Dr. Ruderman.
 

Delayed onset and resolution of rheumatologic immune-related adverse events

“Onset and resolution of rheumatologic adverse events with immunotherapy may be delayed. This is an important point: While skin rash and colitis often show up pretty early in the course of immunotherapy, some of the arthritic events can happen later. They can actually continue after the immunotherapy is stopped,” the rheumatologist said.

Indeed, a retrospective nationwide Canadian study of 117 patients at nine academic centers who developed 136 rheumatic immune-related adverse events in conjunction with cancer immunotherapy found that the mean time to the first such event was 6.8 months into checkpoint inhibitor therapy. The most common rheumatic complication was symmetric polyarthritis, affecting 45 patients. Other rheumatologic immune-related complications included polymyalgia rheumatica in 17 patients, noninflammatory musculoskeletal symptoms in 18, and myositis in 9.

Seventy-six patients were treated with prednisone for a mean of 8.4 months at a maximum dose of 60 mg/day. Forty-two moved up the treatment ladder to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to manage their symptoms. Only two patients required escalation to biologic therapy. A reassuring finding in this relatively small study was that treatment of the patients’ rheumatic complications didn’t appear to worsen the tumor response to immunotherapy: Twenty-three patients experienced tumor progression prior to treatment of their rheumatic disorder, and 14 did so following treatment.
 

Flares of preexisting rheumatic diseases

These tend to occur much earlier in the course of immune checkpoint inhibitor therapy for cancer than de novo immunotherapy-related rheumatic adverse events. In a retrospective Australian study of 12 cancer patients with preexisting rheumatic disease before going on a PD-1 inhibitor and 24 others with no such history, all of whom developed rheumatic adverse events while on the checkpoint inhibitor, the mean time to a flare of preexisting rheumatic disease was 6.2 weeks, compared to 21.5 weeks in patients who experienced a de novo rheumatic adverse event.

Dr. Ruderman supports recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the management of rheumatic immune-related adverse events due to cancer immunotherapy, even though the underlying level of evidence is fairly weak. The recommendations call for the use of csDMARDs when corticosteroids don’t adequately control symptoms. And when the response to csDMARDs is insufficient, the next step is a biologic, preferably a tumor necrosis factor inhibitor or interleukin-6 inhibitor.

“At our institution, the oncologists are a little bit nervous about using biologics in cancer patients, but I think more and more they’re going to have to accept it. And so far there isn’t a ton of evidence that suggests the addition of biologics interferes with the efficacy of the immunotherapy,” the rheumatologist said.

He underscored the critical importance of one of the overarching principles of the EULAR guidelines: the need for interdisciplinary coordination between rheumatologists and oncologists regarding the problem of rheumatologic immune-related adverse events.

“Oncologists aren’t good at managing inflammatory arthritis. I think they really need us,” he said.

Dr. Ruderman reported serving as a consultant to and/or receiving a research grant from nine pharmaceutical companies.

[email protected]

Most checkpoint inhibitor–induced rheumatic complications in cancer patients can be treated successfully with corticosteroids, albeit often at considerably higher doses than rheumatologists typically use in managing rheumatoid arthritis, Eric M. Ruderman, MD, observed at the 2021 Rheumatology Winter Clinical Symposium.

“In RA, we’re all used to the idea that 5 or 10 mg of corticosteroids per day can make a tremendous difference. That’s not always the case here. Patients who develop rheumatic immunotherapy-related adverse events often require 20-30 mg/day to get symptoms under control,” according to Dr. Ruderman, professor of medicine (rheumatology) at Northwestern University, Chicago.

This may be in part because oncologists typically don’t refer affected patients to rheumatologists early on. Guidelines from the National Comprehensive Cancer Network and other oncology groups suggest referral only once a patient develops grade 3 immunotherapy-related rheumatic adverse events, meaning the symptoms significantly impair daily activities, he explained.

Checkpoint inhibitors, which induce T-cell activation to fight the patient’s malignancy, can produce a plethora of off-target effects. These adverse events may involve the skin, heart, lungs, kidneys, eyes, blood, GI tract, and endocrine organs. The drugs also can cause rheumatic or neurologic complications. The most common of these adverse events are colitis and rash. Next most common are arthritis and arthralgia. Rheumatic side effects are most common as a consequence of immunotherapy using a CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, but can also occur in association with programmed cell death protein 1 (PD-1) inhibitors and PD-ligand 1 inhibitors. Arthritis and other rheumatic adverse events are more common in patients undergoing combination therapy.

Some form of frank inflammatory arthritis occurs in 5%-10% of cancer patients undergoing checkpoint inhibitor therapy. This can manifest as an RA-like polyarthritis, spondyloarthritis, polymyalgia rheumatica, necrotizing myositis, or vasculitis. Arthralgia occurs in up to 40% of treated patients.

This immunotherapy-related arthritis is typically more inflammatory than RA. It also has a much more abrupt onset. It is usually seronegative and has no gender predisposition, and the limited available evidence to date suggests there is no increased risk of this complication in checkpoint inhibitor–treated patients with a history of prior rheumatic disease, according to Dr. Ruderman.
 

Delayed onset and resolution of rheumatologic immune-related adverse events

“Onset and resolution of rheumatologic adverse events with immunotherapy may be delayed. This is an important point: While skin rash and colitis often show up pretty early in the course of immunotherapy, some of the arthritic events can happen later. They can actually continue after the immunotherapy is stopped,” the rheumatologist said.

Indeed, a retrospective nationwide Canadian study of 117 patients at nine academic centers who developed 136 rheumatic immune-related adverse events in conjunction with cancer immunotherapy found that the mean time to the first such event was 6.8 months into checkpoint inhibitor therapy. The most common rheumatic complication was symmetric polyarthritis, affecting 45 patients. Other rheumatologic immune-related complications included polymyalgia rheumatica in 17 patients, noninflammatory musculoskeletal symptoms in 18, and myositis in 9.

Seventy-six patients were treated with prednisone for a mean of 8.4 months at a maximum dose of 60 mg/day. Forty-two moved up the treatment ladder to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to manage their symptoms. Only two patients required escalation to biologic therapy. A reassuring finding in this relatively small study was that treatment of the patients’ rheumatic complications didn’t appear to worsen the tumor response to immunotherapy: Twenty-three patients experienced tumor progression prior to treatment of their rheumatic disorder, and 14 did so following treatment.
 

Flares of preexisting rheumatic diseases

These tend to occur much earlier in the course of immune checkpoint inhibitor therapy for cancer than de novo immunotherapy-related rheumatic adverse events. In a retrospective Australian study of 12 cancer patients with preexisting rheumatic disease before going on a PD-1 inhibitor and 24 others with no such history, all of whom developed rheumatic adverse events while on the checkpoint inhibitor, the mean time to a flare of preexisting rheumatic disease was 6.2 weeks, compared to 21.5 weeks in patients who experienced a de novo rheumatic adverse event.

Dr. Ruderman supports recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the management of rheumatic immune-related adverse events due to cancer immunotherapy, even though the underlying level of evidence is fairly weak. The recommendations call for the use of csDMARDs when corticosteroids don’t adequately control symptoms. And when the response to csDMARDs is insufficient, the next step is a biologic, preferably a tumor necrosis factor inhibitor or interleukin-6 inhibitor.

“At our institution, the oncologists are a little bit nervous about using biologics in cancer patients, but I think more and more they’re going to have to accept it. And so far there isn’t a ton of evidence that suggests the addition of biologics interferes with the efficacy of the immunotherapy,” the rheumatologist said.

He underscored the critical importance of one of the overarching principles of the EULAR guidelines: the need for interdisciplinary coordination between rheumatologists and oncologists regarding the problem of rheumatologic immune-related adverse events.

“Oncologists aren’t good at managing inflammatory arthritis. I think they really need us,” he said.

Dr. Ruderman reported serving as a consultant to and/or receiving a research grant from nine pharmaceutical companies.

[email protected]

Most checkpoint inhibitor–induced rheumatic complications in cancer patients can be treated successfully with corticosteroids, albeit often at considerably higher doses than rheumatologists typically use in managing rheumatoid arthritis, Eric M. Ruderman, MD, observed at the 2021 Rheumatology Winter Clinical Symposium.

“In RA, we’re all used to the idea that 5 or 10 mg of corticosteroids per day can make a tremendous difference. That’s not always the case here. Patients who develop rheumatic immunotherapy-related adverse events often require 20-30 mg/day to get symptoms under control,” according to Dr. Ruderman, professor of medicine (rheumatology) at Northwestern University, Chicago.

This may be in part because oncologists typically don’t refer affected patients to rheumatologists early on. Guidelines from the National Comprehensive Cancer Network and other oncology groups suggest referral only once a patient develops grade 3 immunotherapy-related rheumatic adverse events, meaning the symptoms significantly impair daily activities, he explained.

Checkpoint inhibitors, which induce T-cell activation to fight the patient’s malignancy, can produce a plethora of off-target effects. These adverse events may involve the skin, heart, lungs, kidneys, eyes, blood, GI tract, and endocrine organs. The drugs also can cause rheumatic or neurologic complications. The most common of these adverse events are colitis and rash. Next most common are arthritis and arthralgia. Rheumatic side effects are most common as a consequence of immunotherapy using a CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, but can also occur in association with programmed cell death protein 1 (PD-1) inhibitors and PD-ligand 1 inhibitors. Arthritis and other rheumatic adverse events are more common in patients undergoing combination therapy.

Some form of frank inflammatory arthritis occurs in 5%-10% of cancer patients undergoing checkpoint inhibitor therapy. This can manifest as an RA-like polyarthritis, spondyloarthritis, polymyalgia rheumatica, necrotizing myositis, or vasculitis. Arthralgia occurs in up to 40% of treated patients.

This immunotherapy-related arthritis is typically more inflammatory than RA. It also has a much more abrupt onset. It is usually seronegative and has no gender predisposition, and the limited available evidence to date suggests there is no increased risk of this complication in checkpoint inhibitor–treated patients with a history of prior rheumatic disease, according to Dr. Ruderman.
 

Delayed onset and resolution of rheumatologic immune-related adverse events

“Onset and resolution of rheumatologic adverse events with immunotherapy may be delayed. This is an important point: While skin rash and colitis often show up pretty early in the course of immunotherapy, some of the arthritic events can happen later. They can actually continue after the immunotherapy is stopped,” the rheumatologist said.

Indeed, a retrospective nationwide Canadian study of 117 patients at nine academic centers who developed 136 rheumatic immune-related adverse events in conjunction with cancer immunotherapy found that the mean time to the first such event was 6.8 months into checkpoint inhibitor therapy. The most common rheumatic complication was symmetric polyarthritis, affecting 45 patients. Other rheumatologic immune-related complications included polymyalgia rheumatica in 17 patients, noninflammatory musculoskeletal symptoms in 18, and myositis in 9.

Seventy-six patients were treated with prednisone for a mean of 8.4 months at a maximum dose of 60 mg/day. Forty-two moved up the treatment ladder to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to manage their symptoms. Only two patients required escalation to biologic therapy. A reassuring finding in this relatively small study was that treatment of the patients’ rheumatic complications didn’t appear to worsen the tumor response to immunotherapy: Twenty-three patients experienced tumor progression prior to treatment of their rheumatic disorder, and 14 did so following treatment.
 

Flares of preexisting rheumatic diseases

These tend to occur much earlier in the course of immune checkpoint inhibitor therapy for cancer than de novo immunotherapy-related rheumatic adverse events. In a retrospective Australian study of 12 cancer patients with preexisting rheumatic disease before going on a PD-1 inhibitor and 24 others with no such history, all of whom developed rheumatic adverse events while on the checkpoint inhibitor, the mean time to a flare of preexisting rheumatic disease was 6.2 weeks, compared to 21.5 weeks in patients who experienced a de novo rheumatic adverse event.

Dr. Ruderman supports recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the management of rheumatic immune-related adverse events due to cancer immunotherapy, even though the underlying level of evidence is fairly weak. The recommendations call for the use of csDMARDs when corticosteroids don’t adequately control symptoms. And when the response to csDMARDs is insufficient, the next step is a biologic, preferably a tumor necrosis factor inhibitor or interleukin-6 inhibitor.

“At our institution, the oncologists are a little bit nervous about using biologics in cancer patients, but I think more and more they’re going to have to accept it. And so far there isn’t a ton of evidence that suggests the addition of biologics interferes with the efficacy of the immunotherapy,” the rheumatologist said.

He underscored the critical importance of one of the overarching principles of the EULAR guidelines: the need for interdisciplinary coordination between rheumatologists and oncologists regarding the problem of rheumatologic immune-related adverse events.

“Oncologists aren’t good at managing inflammatory arthritis. I think they really need us,” he said.

Dr. Ruderman reported serving as a consultant to and/or receiving a research grant from nine pharmaceutical companies.

[email protected]