Clinical Edge Journal Scan

Several studies published this month have shed some more light on the treatment and prognosis of certain molecular subgroups such as FLT3, spliceasome mutations and IDH mutation. A study from MD Anderson Cancer Center (MDACC) demonstrated the efficacy of FLT33 inhibitors in the treatment of patients with very low allelic burden. Patients who recived both a FMS-like tyrosine kinase inhibitor (FLT3i) during induction and an allogeneic HCT at time of first remission had better 5 year overall survival (OS) (100%) than those who received neither (27%). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. None of the patients who received a FLT3i had detectable FLT3 at time of relapse, compared to 67% for those who did not. The main weakness of the study is the small number of patients (total of 50 patients). This study however does provide some provocative data regarding the validity of the FLT3 allelic ratio in decisions regarding treatment and prognosis. The results of this study need to be validated in a larger cohort of patients.

A study by Lachowiez et al, further refined the prognostic significance of spliceosome mutations in patients treated with ven + HMA. Of the 119 patients, 39 had spliceosome mutations. The overall response and prognosis was not different between patients with and without spliceosome mutations. However, SRSF2 was associated with IDH2 mutation and the median OS was not reached vs, patient with U2AF1 who had a higher association with RAS mutations (OS 8 months). The prognostic role of standard cytotoxic chemotherapy in improving the outcome of patients with an IDH mutation was studied by the group. In a re-evaluation of the randomized trial comparing the addition of fludarabine or cladrbaine to standard 7 +3, 50 patients with an IDH mutation were evaluated. Patients with an IDH mutation who received cladribine. IDH2 mutation had a positive impact on OS in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Although hypomethylating agents + venetoclax (HMA +ven) have shown efficacy in multiple patient subgroups, the outcome of patients with post-MPN acute myeloid leukemia (AML) remains poor even with HMA + ven. In a retrospective study, 31 patients with post MPN AML were treated with HMA + ven. The overall survival for patients with relapsed post MPN AML was 3 months with none of the 9 patients achieving a CR/CRi. As for the patients with previously untreated post MPN-AML, the median survival was still poor at 8 months with 43% achieving CR/CRi. This study highlights the large unmet need in this patient population. In comparison, in a retrospective study by Piccini et al, of the 47 patients with relapsed/refractory (R/R) AML treated with venetoclax based regimens the composite CR rate was 55%. These outcomes are similar to other studies of venetoclax based regimens in patients with R/R AML. 

In a retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) registry, the outcomes of patients receiving mismatched unrelated donor (MMUD) with post transplant cyclophosphamide (PTCy) had better outcomes compared to patients receiving cord blood transplantation (CBT). The 2 year leukemia free survival (LFS) for CBT vs MMUD was 42.8% vs 60.5% and OS was 46.85 vs 62.8%. This retrospective study demonstrated that PTCy can improve the outcomes of patients receiving of MMUD (Dholaria B et al. J Hematol Oncol. 2021 May).

Several studies published this month have shed some more light on the treatment and prognosis of certain molecular subgroups such as FLT3, spliceasome mutations and IDH mutation. A study from MD Anderson Cancer Center (MDACC) demonstrated the efficacy of FLT33 inhibitors in the treatment of patients with very low allelic burden. Patients who recived both a FMS-like tyrosine kinase inhibitor (FLT3i) during induction and an allogeneic HCT at time of first remission had better 5 year overall survival (OS) (100%) than those who received neither (27%). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. None of the patients who received a FLT3i had detectable FLT3 at time of relapse, compared to 67% for those who did not. The main weakness of the study is the small number of patients (total of 50 patients). This study however does provide some provocative data regarding the validity of the FLT3 allelic ratio in decisions regarding treatment and prognosis. The results of this study need to be validated in a larger cohort of patients.

A study by Lachowiez et al, further refined the prognostic significance of spliceosome mutations in patients treated with ven + HMA. Of the 119 patients, 39 had spliceosome mutations. The overall response and prognosis was not different between patients with and without spliceosome mutations. However, SRSF2 was associated with IDH2 mutation and the median OS was not reached vs, patient with U2AF1 who had a higher association with RAS mutations (OS 8 months). The prognostic role of standard cytotoxic chemotherapy in improving the outcome of patients with an IDH mutation was studied by the group. In a re-evaluation of the randomized trial comparing the addition of fludarabine or cladrbaine to standard 7 +3, 50 patients with an IDH mutation were evaluated. Patients with an IDH mutation who received cladribine. IDH2 mutation had a positive impact on OS in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Although hypomethylating agents + venetoclax (HMA +ven) have shown efficacy in multiple patient subgroups, the outcome of patients with post-MPN acute myeloid leukemia (AML) remains poor even with HMA + ven. In a retrospective study, 31 patients with post MPN AML were treated with HMA + ven. The overall survival for patients with relapsed post MPN AML was 3 months with none of the 9 patients achieving a CR/CRi. As for the patients with previously untreated post MPN-AML, the median survival was still poor at 8 months with 43% achieving CR/CRi. This study highlights the large unmet need in this patient population. In comparison, in a retrospective study by Piccini et al, of the 47 patients with relapsed/refractory (R/R) AML treated with venetoclax based regimens the composite CR rate was 55%. These outcomes are similar to other studies of venetoclax based regimens in patients with R/R AML. 

In a retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) registry, the outcomes of patients receiving mismatched unrelated donor (MMUD) with post transplant cyclophosphamide (PTCy) had better outcomes compared to patients receiving cord blood transplantation (CBT). The 2 year leukemia free survival (LFS) for CBT vs MMUD was 42.8% vs 60.5% and OS was 46.85 vs 62.8%. This retrospective study demonstrated that PTCy can improve the outcomes of patients receiving of MMUD (Dholaria B et al. J Hematol Oncol. 2021 May).

Several studies published this month have shed some more light on the treatment and prognosis of certain molecular subgroups such as FLT3, spliceasome mutations and IDH mutation. A study from MD Anderson Cancer Center (MDACC) demonstrated the efficacy of FLT33 inhibitors in the treatment of patients with very low allelic burden. Patients who recived both a FMS-like tyrosine kinase inhibitor (FLT3i) during induction and an allogeneic HCT at time of first remission had better 5 year overall survival (OS) (100%) than those who received neither (27%). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. None of the patients who received a FLT3i had detectable FLT3 at time of relapse, compared to 67% for those who did not. The main weakness of the study is the small number of patients (total of 50 patients). This study however does provide some provocative data regarding the validity of the FLT3 allelic ratio in decisions regarding treatment and prognosis. The results of this study need to be validated in a larger cohort of patients.

A study by Lachowiez et al, further refined the prognostic significance of spliceosome mutations in patients treated with ven + HMA. Of the 119 patients, 39 had spliceosome mutations. The overall response and prognosis was not different between patients with and without spliceosome mutations. However, SRSF2 was associated with IDH2 mutation and the median OS was not reached vs, patient with U2AF1 who had a higher association with RAS mutations (OS 8 months). The prognostic role of standard cytotoxic chemotherapy in improving the outcome of patients with an IDH mutation was studied by the group. In a re-evaluation of the randomized trial comparing the addition of fludarabine or cladrbaine to standard 7 +3, 50 patients with an IDH mutation were evaluated. Patients with an IDH mutation who received cladribine. IDH2 mutation had a positive impact on OS in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Although hypomethylating agents + venetoclax (HMA +ven) have shown efficacy in multiple patient subgroups, the outcome of patients with post-MPN acute myeloid leukemia (AML) remains poor even with HMA + ven. In a retrospective study, 31 patients with post MPN AML were treated with HMA + ven. The overall survival for patients with relapsed post MPN AML was 3 months with none of the 9 patients achieving a CR/CRi. As for the patients with previously untreated post MPN-AML, the median survival was still poor at 8 months with 43% achieving CR/CRi. This study highlights the large unmet need in this patient population. In comparison, in a retrospective study by Piccini et al, of the 47 patients with relapsed/refractory (R/R) AML treated with venetoclax based regimens the composite CR rate was 55%. These outcomes are similar to other studies of venetoclax based regimens in patients with R/R AML. 

In a retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) registry, the outcomes of patients receiving mismatched unrelated donor (MMUD) with post transplant cyclophosphamide (PTCy) had better outcomes compared to patients receiving cord blood transplantation (CBT). The 2 year leukemia free survival (LFS) for CBT vs MMUD was 42.8% vs 60.5% and OS was 46.85 vs 62.8%. This retrospective study demonstrated that PTCy can improve the outcomes of patients receiving of MMUD (Dholaria B et al. J Hematol Oncol. 2021 May).

Key clinical point: Protein tyrosine phosphatase receptor gamma (PTPRG), a tumor suppressor gene, could serve as a new biomarker to evaluate therapeutic response to tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML).

Major finding: In patients with CML, PTPRG expression was significantly lower at diagnosis vs. follow-up (P less than .001). Patients with optimal response to TKI had significantly higher PTPRG expression during follow-up vs. diagnosis (P less than .0005); however, no difference was observed in patients with a failed response to TKI (P = .312).

Study details: This study assessed PTPRG expression in 21 patients with CML (chronic phase, n=18; accelerated phase, n=3) treated with imatinib (n=12) or nilotinib (n=9) and 7 healthy individuals.

Disclosures: This study was funded by the Qatar National Research Fund, and open access funding was enabled by the Qatar National Library. The authors declared no conflicts of interest.

Source: Ismail MA et al. Sci Rep. 2021 Apr 23. doi: 10.1038/s41598-021-86875-y.

Key clinical point: Protein tyrosine phosphatase receptor gamma (PTPRG), a tumor suppressor gene, could serve as a new biomarker to evaluate therapeutic response to tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML).

Major finding: In patients with CML, PTPRG expression was significantly lower at diagnosis vs. follow-up (P less than .001). Patients with optimal response to TKI had significantly higher PTPRG expression during follow-up vs. diagnosis (P less than .0005); however, no difference was observed in patients with a failed response to TKI (P = .312).

Study details: This study assessed PTPRG expression in 21 patients with CML (chronic phase, n=18; accelerated phase, n=3) treated with imatinib (n=12) or nilotinib (n=9) and 7 healthy individuals.

Disclosures: This study was funded by the Qatar National Research Fund, and open access funding was enabled by the Qatar National Library. The authors declared no conflicts of interest.

Source: Ismail MA et al. Sci Rep. 2021 Apr 23. doi: 10.1038/s41598-021-86875-y.

Key clinical point: Protein tyrosine phosphatase receptor gamma (PTPRG), a tumor suppressor gene, could serve as a new biomarker to evaluate therapeutic response to tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML).

Major finding: In patients with CML, PTPRG expression was significantly lower at diagnosis vs. follow-up (P less than .001). Patients with optimal response to TKI had significantly higher PTPRG expression during follow-up vs. diagnosis (P less than .0005); however, no difference was observed in patients with a failed response to TKI (P = .312).

Study details: This study assessed PTPRG expression in 21 patients with CML (chronic phase, n=18; accelerated phase, n=3) treated with imatinib (n=12) or nilotinib (n=9) and 7 healthy individuals.

Disclosures: This study was funded by the Qatar National Research Fund, and open access funding was enabled by the Qatar National Library. The authors declared no conflicts of interest.

Source: Ismail MA et al. Sci Rep. 2021 Apr 23. doi: 10.1038/s41598-021-86875-y.

Key clinical point: High cancerous inhibitor of protein phosphatase 2A (CIP2A) levels at diagnosis predicts subsequent disease progression and treatment failure in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with imatinib or dasatinib.

Major finding: High vs. low CIP2A levels were associated with poor progression-free survival (P = .04) and freedom from progression (P = .03). Patients with high vs. low CIP2A levels had a higher chance of treatment failure at 5 years (41% vs. 7.5%; P = .002) in both imatinib- (45% vs. 11%; P = .02) and dasatinib-treated (36% vs. 4%; P = .007) patients.

Study details: Data come from an analysis of 172 patients with newly diagnosed CML-CP enrolled in phase 3 SPIRIT2 trial who were randomly allocated to frontline imatinib (n=90) or dasatinib (n=82).

Disclosures: This study was funded by Bristol Myers Squibb (BMS). The lead author reported research support and/or honoraria from Novartis, BMS, and Pfizer. Other authors declared no conflicts of interest.

Source: Clark RE et al. Cancers (Basel). 2021 Apr 29. doi: 10.3390/cancers13092155.

Key clinical point: High cancerous inhibitor of protein phosphatase 2A (CIP2A) levels at diagnosis predicts subsequent disease progression and treatment failure in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with imatinib or dasatinib.

Major finding: High vs. low CIP2A levels were associated with poor progression-free survival (P = .04) and freedom from progression (P = .03). Patients with high vs. low CIP2A levels had a higher chance of treatment failure at 5 years (41% vs. 7.5%; P = .002) in both imatinib- (45% vs. 11%; P = .02) and dasatinib-treated (36% vs. 4%; P = .007) patients.

Study details: Data come from an analysis of 172 patients with newly diagnosed CML-CP enrolled in phase 3 SPIRIT2 trial who were randomly allocated to frontline imatinib (n=90) or dasatinib (n=82).

Disclosures: This study was funded by Bristol Myers Squibb (BMS). The lead author reported research support and/or honoraria from Novartis, BMS, and Pfizer. Other authors declared no conflicts of interest.

Source: Clark RE et al. Cancers (Basel). 2021 Apr 29. doi: 10.3390/cancers13092155.

Key clinical point: High cancerous inhibitor of protein phosphatase 2A (CIP2A) levels at diagnosis predicts subsequent disease progression and treatment failure in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with imatinib or dasatinib.

Major finding: High vs. low CIP2A levels were associated with poor progression-free survival (P = .04) and freedom from progression (P = .03). Patients with high vs. low CIP2A levels had a higher chance of treatment failure at 5 years (41% vs. 7.5%; P = .002) in both imatinib- (45% vs. 11%; P = .02) and dasatinib-treated (36% vs. 4%; P = .007) patients.

Study details: Data come from an analysis of 172 patients with newly diagnosed CML-CP enrolled in phase 3 SPIRIT2 trial who were randomly allocated to frontline imatinib (n=90) or dasatinib (n=82).

Disclosures: This study was funded by Bristol Myers Squibb (BMS). The lead author reported research support and/or honoraria from Novartis, BMS, and Pfizer. Other authors declared no conflicts of interest.

Source: Clark RE et al. Cancers (Basel). 2021 Apr 29. doi: 10.3390/cancers13092155.

Key clinical point: Patients with chronic-phase chronic myeloid leukemia (CML-CP) receiving a second-generation tyrosine kinase inhibitor (TKI) frontline and fulfilling eligibility criteria for European LeukemiaNet 2020 treatment-free remission (TFR) recommendations had the highest molecular recurrence-free survival (MRFS) after TKI discontinuation.

Major finding: MRFS at 2 and 5 years were 51.8% and 43.8%, respectively. MRFS was significantly higher in patients who fulfilled TFR recommendations vs. those who did not (P = .005). Molecular recurrence was highest in patients treated with frontline imatinib not fulfilling TFR recommendations and lowest in patients treated with a second-generation TKI and who fulfilled the eligibility criteria.

Study details: This retrospective study assessed TFR eligibility and outcomes in 398 patients with newly diagnosed CML-CP treated with either imatinib (73%) or a second- or third-generation TKI (27%) as frontline therapy.

Disclosures: No specific funding source was identified. Some investigators including the lead author reported ties with various pharmaceutical companies. The authors declared no conflicts of interest.

Source: Etienne G et al. Cancer Med. 2021 May 14. doi: 10.1002/cam4.3921.

Key clinical point: Patients with chronic-phase chronic myeloid leukemia (CML-CP) receiving a second-generation tyrosine kinase inhibitor (TKI) frontline and fulfilling eligibility criteria for European LeukemiaNet 2020 treatment-free remission (TFR) recommendations had the highest molecular recurrence-free survival (MRFS) after TKI discontinuation.

Major finding: MRFS at 2 and 5 years were 51.8% and 43.8%, respectively. MRFS was significantly higher in patients who fulfilled TFR recommendations vs. those who did not (P = .005). Molecular recurrence was highest in patients treated with frontline imatinib not fulfilling TFR recommendations and lowest in patients treated with a second-generation TKI and who fulfilled the eligibility criteria.

Study details: This retrospective study assessed TFR eligibility and outcomes in 398 patients with newly diagnosed CML-CP treated with either imatinib (73%) or a second- or third-generation TKI (27%) as frontline therapy.

Disclosures: No specific funding source was identified. Some investigators including the lead author reported ties with various pharmaceutical companies. The authors declared no conflicts of interest.

Source: Etienne G et al. Cancer Med. 2021 May 14. doi: 10.1002/cam4.3921.

Key clinical point: Patients with chronic-phase chronic myeloid leukemia (CML-CP) receiving a second-generation tyrosine kinase inhibitor (TKI) frontline and fulfilling eligibility criteria for European LeukemiaNet 2020 treatment-free remission (TFR) recommendations had the highest molecular recurrence-free survival (MRFS) after TKI discontinuation.

Major finding: MRFS at 2 and 5 years were 51.8% and 43.8%, respectively. MRFS was significantly higher in patients who fulfilled TFR recommendations vs. those who did not (P = .005). Molecular recurrence was highest in patients treated with frontline imatinib not fulfilling TFR recommendations and lowest in patients treated with a second-generation TKI and who fulfilled the eligibility criteria.

Study details: This retrospective study assessed TFR eligibility and outcomes in 398 patients with newly diagnosed CML-CP treated with either imatinib (73%) or a second- or third-generation TKI (27%) as frontline therapy.

Disclosures: No specific funding source was identified. Some investigators including the lead author reported ties with various pharmaceutical companies. The authors declared no conflicts of interest.

Source: Etienne G et al. Cancer Med. 2021 May 14. doi: 10.1002/cam4.3921.

Key clinical point: Cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) improved tyrosine kinase inhibitor (TKI)-related fatigue in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Patients receiving 18-week CBT-TTF vs. control reported improvements in physical (P = .023), mental (P = .015), and social activity (P = .001), along with enhanced cognitions including self-efficacy (P = .001), helplessness (P = .003), fatigue catastrophizing and focusing on symptoms (both P less than .001).

Study details: Findings are from secondary analysis of a trial including 36 adults with CML-CP treated with a TKI, who reported moderate to severe fatigue and were randomly allocated to receive either CBT-TTF (n=22) or waitlist control (n=14).

Disclosures: This study was funded by the National Cancer Institute. Some coinvestigators reported grants, consultancy, advisory, and speakers’ bureau memberships from various pharmaceutical companies.

Source: Hyland KA et al. Ann Behav Med. 2021 May 15. doi: 10.1093/abm/kaab035.

Key clinical point: Cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) improved tyrosine kinase inhibitor (TKI)-related fatigue in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Patients receiving 18-week CBT-TTF vs. control reported improvements in physical (P = .023), mental (P = .015), and social activity (P = .001), along with enhanced cognitions including self-efficacy (P = .001), helplessness (P = .003), fatigue catastrophizing and focusing on symptoms (both P less than .001).

Study details: Findings are from secondary analysis of a trial including 36 adults with CML-CP treated with a TKI, who reported moderate to severe fatigue and were randomly allocated to receive either CBT-TTF (n=22) or waitlist control (n=14).

Disclosures: This study was funded by the National Cancer Institute. Some coinvestigators reported grants, consultancy, advisory, and speakers’ bureau memberships from various pharmaceutical companies.

Source: Hyland KA et al. Ann Behav Med. 2021 May 15. doi: 10.1093/abm/kaab035.

Key clinical point: Cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) improved tyrosine kinase inhibitor (TKI)-related fatigue in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Patients receiving 18-week CBT-TTF vs. control reported improvements in physical (P = .023), mental (P = .015), and social activity (P = .001), along with enhanced cognitions including self-efficacy (P = .001), helplessness (P = .003), fatigue catastrophizing and focusing on symptoms (both P less than .001).

Study details: Findings are from secondary analysis of a trial including 36 adults with CML-CP treated with a TKI, who reported moderate to severe fatigue and were randomly allocated to receive either CBT-TTF (n=22) or waitlist control (n=14).

Disclosures: This study was funded by the National Cancer Institute. Some coinvestigators reported grants, consultancy, advisory, and speakers’ bureau memberships from various pharmaceutical companies.

Source: Hyland KA et al. Ann Behav Med. 2021 May 15. doi: 10.1093/abm/kaab035.

Key clinical point: Findings from routine clinical practice are in concordance with results from clinical trials and confirm the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs) or had T315I mutation. No new safety signals were identified.

Major finding: During a median follow-up of 15 months, major molecular response was achieved in 58% of patients with CML. Estimated 3-year overall survival and progression-free survival were 85.3% and 81.6%, respectively. Treatment termination because of adverse events occurred in 8 patients with CML.

Study details: Findings are from a prospective observational study including 33 patients with CML and 17 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Patients were initiated on ponatinib following intolerance, relapse, or refractoriness to prior TKIs, disease progression, or T315I mutation.

Disclosures: This study was funded by Incyte Biosciences Benelux BV. Some investigators reported research funding, advisory board memberships, consultancy, honoraria, travel expenses, and membership of the board of directors for various pharmaceutical companies including Incyte Biosciences Benelux BV.

Source: Devos T et al. Ann Hematol. 2021 May 4. doi: 10.1007/s00277-021-04507-x.

Key clinical point: Findings from routine clinical practice are in concordance with results from clinical trials and confirm the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs) or had T315I mutation. No new safety signals were identified.

Major finding: During a median follow-up of 15 months, major molecular response was achieved in 58% of patients with CML. Estimated 3-year overall survival and progression-free survival were 85.3% and 81.6%, respectively. Treatment termination because of adverse events occurred in 8 patients with CML.

Study details: Findings are from a prospective observational study including 33 patients with CML and 17 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Patients were initiated on ponatinib following intolerance, relapse, or refractoriness to prior TKIs, disease progression, or T315I mutation.

Disclosures: This study was funded by Incyte Biosciences Benelux BV. Some investigators reported research funding, advisory board memberships, consultancy, honoraria, travel expenses, and membership of the board of directors for various pharmaceutical companies including Incyte Biosciences Benelux BV.

Source: Devos T et al. Ann Hematol. 2021 May 4. doi: 10.1007/s00277-021-04507-x.

Key clinical point: Findings from routine clinical practice are in concordance with results from clinical trials and confirm the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs) or had T315I mutation. No new safety signals were identified.

Major finding: During a median follow-up of 15 months, major molecular response was achieved in 58% of patients with CML. Estimated 3-year overall survival and progression-free survival were 85.3% and 81.6%, respectively. Treatment termination because of adverse events occurred in 8 patients with CML.

Study details: Findings are from a prospective observational study including 33 patients with CML and 17 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Patients were initiated on ponatinib following intolerance, relapse, or refractoriness to prior TKIs, disease progression, or T315I mutation.

Disclosures: This study was funded by Incyte Biosciences Benelux BV. Some investigators reported research funding, advisory board memberships, consultancy, honoraria, travel expenses, and membership of the board of directors for various pharmaceutical companies including Incyte Biosciences Benelux BV.

Source: Devos T et al. Ann Hematol. 2021 May 4. doi: 10.1007/s00277-021-04507-x.

Key clinical point: Single nucleotide polymorphisms (SNPs) in the major multidrug resistance (MDR)-ATP-binding cassette (ABC) transporter genes, ABCB1, ABCC2, and ABCG2, influenced the achievement of molecular response (MR)3 and MR4 in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with nilotinib.

Major finding: Patients with ABCB1 rs1045642 TT (P = .01) or ABCC2 rs3740066 CT (P = .004) and CC (P = .02) genotypes achieved significantly higher rates of MR3 in a shorter period. Conversely, patients with ABCG2 rs2231137 GG genotype had a lower probability of achieving MR3 (P = .005). ABCC2 rs3740066 CC (P = .02) and ABCB1 rs1045642 CC (P = .007) and TT (P = .003) genotypes were associated with higher rates of MR4 achievement.

Study details: This observational study assessed 7 SNPs in 4 ABC transporter genes (ABCB1, ABCC1, ABCC2, and ABCG2) in 90 Caucasian adult patients with CML-CP treated with first-or second-line nilotinib.

Disclosures: This study was supported in part by AIL Pesaro Onlus. The authors declared no conflicts of interest.

Source: Loscocco F et al. Front Oncol. 2021 May 13. doi: 10.3389/fonc.2021.672287.

Key clinical point: Single nucleotide polymorphisms (SNPs) in the major multidrug resistance (MDR)-ATP-binding cassette (ABC) transporter genes, ABCB1, ABCC2, and ABCG2, influenced the achievement of molecular response (MR)3 and MR4 in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with nilotinib.

Major finding: Patients with ABCB1 rs1045642 TT (P = .01) or ABCC2 rs3740066 CT (P = .004) and CC (P = .02) genotypes achieved significantly higher rates of MR3 in a shorter period. Conversely, patients with ABCG2 rs2231137 GG genotype had a lower probability of achieving MR3 (P = .005). ABCC2 rs3740066 CC (P = .02) and ABCB1 rs1045642 CC (P = .007) and TT (P = .003) genotypes were associated with higher rates of MR4 achievement.

Study details: This observational study assessed 7 SNPs in 4 ABC transporter genes (ABCB1, ABCC1, ABCC2, and ABCG2) in 90 Caucasian adult patients with CML-CP treated with first-or second-line nilotinib.

Disclosures: This study was supported in part by AIL Pesaro Onlus. The authors declared no conflicts of interest.

Source: Loscocco F et al. Front Oncol. 2021 May 13. doi: 10.3389/fonc.2021.672287.

Key clinical point: Single nucleotide polymorphisms (SNPs) in the major multidrug resistance (MDR)-ATP-binding cassette (ABC) transporter genes, ABCB1, ABCC2, and ABCG2, influenced the achievement of molecular response (MR)3 and MR4 in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with nilotinib.

Major finding: Patients with ABCB1 rs1045642 TT (P = .01) or ABCC2 rs3740066 CT (P = .004) and CC (P = .02) genotypes achieved significantly higher rates of MR3 in a shorter period. Conversely, patients with ABCG2 rs2231137 GG genotype had a lower probability of achieving MR3 (P = .005). ABCC2 rs3740066 CC (P = .02) and ABCB1 rs1045642 CC (P = .007) and TT (P = .003) genotypes were associated with higher rates of MR4 achievement.

Study details: This observational study assessed 7 SNPs in 4 ABC transporter genes (ABCB1, ABCC1, ABCC2, and ABCG2) in 90 Caucasian adult patients with CML-CP treated with first-or second-line nilotinib.

Disclosures: This study was supported in part by AIL Pesaro Onlus. The authors declared no conflicts of interest.

Source: Loscocco F et al. Front Oncol. 2021 May 13. doi: 10.3389/fonc.2021.672287.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CML-CP), imatinib treatment for at least 6 years and molecular response 4 (MR4) duration of a minimum of 4.5 years may be optimal for higher treatment-free remission (TFR) success after imatinib discontinuation.

Major finding: Patients with imatinib treatment duration of 6 years or more vs. less than 6 years (61.8% vs. 36.0%; P = .01) and those with MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) had a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Study details: This prospective study reported findings from the TRAD study including 131 patients with CML-CP. Patients were treated with imatinib for at least 3 years (range, 3.0-17.5 years) and had a minimum of 2 years of MR4 or deeper response (range, 2.0-15.8 years) before imatinib discontinuation.

Disclosures: This study was supported by BMS Canada and the Princess Margaret Cancer Foundation. The lead author reported research funding from BMS and Novartis.

Source: Kim DDH et al. Br J Haematol. 2021 Apr 20. doi: 10.1111/bjh.17447.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CML-CP), imatinib treatment for at least 6 years and molecular response 4 (MR4) duration of a minimum of 4.5 years may be optimal for higher treatment-free remission (TFR) success after imatinib discontinuation.

Major finding: Patients with imatinib treatment duration of 6 years or more vs. less than 6 years (61.8% vs. 36.0%; P = .01) and those with MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) had a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Study details: This prospective study reported findings from the TRAD study including 131 patients with CML-CP. Patients were treated with imatinib for at least 3 years (range, 3.0-17.5 years) and had a minimum of 2 years of MR4 or deeper response (range, 2.0-15.8 years) before imatinib discontinuation.

Disclosures: This study was supported by BMS Canada and the Princess Margaret Cancer Foundation. The lead author reported research funding from BMS and Novartis.

Source: Kim DDH et al. Br J Haematol. 2021 Apr 20. doi: 10.1111/bjh.17447.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CML-CP), imatinib treatment for at least 6 years and molecular response 4 (MR4) duration of a minimum of 4.5 years may be optimal for higher treatment-free remission (TFR) success after imatinib discontinuation.

Major finding: Patients with imatinib treatment duration of 6 years or more vs. less than 6 years (61.8% vs. 36.0%; P = .01) and those with MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) had a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Study details: This prospective study reported findings from the TRAD study including 131 patients with CML-CP. Patients were treated with imatinib for at least 3 years (range, 3.0-17.5 years) and had a minimum of 2 years of MR4 or deeper response (range, 2.0-15.8 years) before imatinib discontinuation.

Disclosures: This study was supported by BMS Canada and the Princess Margaret Cancer Foundation. The lead author reported research funding from BMS and Novartis.

Source: Kim DDH et al. Br J Haematol. 2021 Apr 20. doi: 10.1111/bjh.17447.

Key clinical point: Response and survival with current therapies remain poor in patients with atypical chronic myeloid leukemia (aCML), with allogeneic stem cell transplantation (allo-SCT) being the only treatment associated with improved survival.

Major finding: Overall response rate was 29%, with only 3 patients achieving a complete response. The median overall survival (OS) was 25 (95% confidence interval, 20.0-30.0) months, with OS being worst in patients receiving intensive chemotherapy than those receiving hypomethylating agents, ruxolitinib, or hydroxyurea. Allo-SCT was associated with improved survival (hazard ratio, 0.144; P = .007).

Study details: This retrospective study included 65 patients (median age, 67 years) with aCML.

Disclosures: This study was funded by grants from The University of Texas MD Anderson Cancer Center. Some investigators reported financial and/or nonfinancial ties with various pharmaceutical companies.

Source: Montalban-Bravo G et al. Cancer. 2021 Apr 29. doi: 10.1002/cncr.33622.

Key clinical point: Response and survival with current therapies remain poor in patients with atypical chronic myeloid leukemia (aCML), with allogeneic stem cell transplantation (allo-SCT) being the only treatment associated with improved survival.

Major finding: Overall response rate was 29%, with only 3 patients achieving a complete response. The median overall survival (OS) was 25 (95% confidence interval, 20.0-30.0) months, with OS being worst in patients receiving intensive chemotherapy than those receiving hypomethylating agents, ruxolitinib, or hydroxyurea. Allo-SCT was associated with improved survival (hazard ratio, 0.144; P = .007).

Study details: This retrospective study included 65 patients (median age, 67 years) with aCML.

Disclosures: This study was funded by grants from The University of Texas MD Anderson Cancer Center. Some investigators reported financial and/or nonfinancial ties with various pharmaceutical companies.

Source: Montalban-Bravo G et al. Cancer. 2021 Apr 29. doi: 10.1002/cncr.33622.

Key clinical point: Response and survival with current therapies remain poor in patients with atypical chronic myeloid leukemia (aCML), with allogeneic stem cell transplantation (allo-SCT) being the only treatment associated with improved survival.

Major finding: Overall response rate was 29%, with only 3 patients achieving a complete response. The median overall survival (OS) was 25 (95% confidence interval, 20.0-30.0) months, with OS being worst in patients receiving intensive chemotherapy than those receiving hypomethylating agents, ruxolitinib, or hydroxyurea. Allo-SCT was associated with improved survival (hazard ratio, 0.144; P = .007).

Study details: This retrospective study included 65 patients (median age, 67 years) with aCML.

Disclosures: This study was funded by grants from The University of Texas MD Anderson Cancer Center. Some investigators reported financial and/or nonfinancial ties with various pharmaceutical companies.

Source: Montalban-Bravo G et al. Cancer. 2021 Apr 29. doi: 10.1002/cncr.33622.

Key clinical point: Treatment-free remission (TFR) was durable in a large proportion of patients with chronic-phase chronic myeloid leukemia (CML-CP) who switched to nilotinib from imatinib. However, careful management of adverse events (AEs) is required in patients reinitiating nilotinib after TFR.

Major finding: At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase (67.8% vs. 28.2%) including a higher frequency of cardiovascular events (27.1% vs. 6.1%).

Study details: Findings are from an updated analysis of phase 2 ENESTop trial including patients with CML-CP who achieved sustained deep molecular response only after switching from imatinib to nilotinib. TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author reported financial and nonfinancial ties with Bristol Myers Squibb and Novartis. Some investigators reported ties with various pharmaceutical companies including Novartis.

Source: Hughes TP et al. Leukemia. 2021 May 12. doi: 10.1038/s41375-021-01260-y.

Key clinical point: Treatment-free remission (TFR) was durable in a large proportion of patients with chronic-phase chronic myeloid leukemia (CML-CP) who switched to nilotinib from imatinib. However, careful management of adverse events (AEs) is required in patients reinitiating nilotinib after TFR.

Major finding: At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase (67.8% vs. 28.2%) including a higher frequency of cardiovascular events (27.1% vs. 6.1%).

Study details: Findings are from an updated analysis of phase 2 ENESTop trial including patients with CML-CP who achieved sustained deep molecular response only after switching from imatinib to nilotinib. TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author reported financial and nonfinancial ties with Bristol Myers Squibb and Novartis. Some investigators reported ties with various pharmaceutical companies including Novartis.

Source: Hughes TP et al. Leukemia. 2021 May 12. doi: 10.1038/s41375-021-01260-y.

Key clinical point: Treatment-free remission (TFR) was durable in a large proportion of patients with chronic-phase chronic myeloid leukemia (CML-CP) who switched to nilotinib from imatinib. However, careful management of adverse events (AEs) is required in patients reinitiating nilotinib after TFR.

Major finding: At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase (67.8% vs. 28.2%) including a higher frequency of cardiovascular events (27.1% vs. 6.1%).

Study details: Findings are from an updated analysis of phase 2 ENESTop trial including patients with CML-CP who achieved sustained deep molecular response only after switching from imatinib to nilotinib. TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author reported financial and nonfinancial ties with Bristol Myers Squibb and Novartis. Some investigators reported ties with various pharmaceutical companies including Novartis.

Source: Hughes TP et al. Leukemia. 2021 May 12. doi: 10.1038/s41375-021-01260-y.