European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

Hochhaus, Andreas; Baccarani, Michele; Silver, Richard T.; Schiffer, Charles A.; Apperley, Jane F.; Cervantes, Francisco; Clark, Richard E.; Cortés, Jorge E.; Deininger, Michael W.; Guilhot, François; Hjorth‐Hansen, Henrik; Hughes, Timothy P.; Janssen, Jeroen; Kantarjian, Hagop M.; Kim, Dong-Wook; Larson, Richard A.; Lipton, Jeffrey H.; Mahon, François‐Xavier; Mayer, Jiřı́; Nicolini, Franck E.; Niederwieser, Dietger; Pane, Fabrizio; Radich, Jerald P.; Réa, Delphine; Richter, Johan; Rosti, Gianantonio; Rousselot, Philippe; Saglio, Giuseppe; Saußele, Susanne; Soverini, Simona; Steegmann, Juan Luis; Turkina, Anna; Zaritskey, Andrey; Hehlmann, Rüediger

doi:10.1038/s41375-020-0776-2

Cited by 1,101 publications

(1,671 citation statements)

References 137 publications

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“…Standard response criteria for CML were used as previously described 6,7 . Briefly, complete hematologic response (CHR) included normalization of the blast percentage in PB and BM (≤5% BM blasts); leukocytes <10 × 10 9 /L; resolution of signs and symptoms of CML; normalization of PB differential (with no peripheral blasts, promyelocytes, or myelocytes); and platelet count <450 × 10 9 /L.…”

Section: Methodsmentioning

confidence: 99%

“…When thrombocytopenia (platelets <100 × 10 9 /L) was present before treatment, platelet count normalization to a level > 100 × 10 9 /L was necessary for classification of the response as CHR. Patients who had a normal platelet count before initiating treatment, but who later developed thrombocytopenia while on therapy could be considered to have CHR if all other criteria for CHR were met 6,7 …”

Section: Methodsmentioning

confidence: 99%

“…Cytogenetic responses were categorized as no response if the percentage of Philadelphia chromosome‐positive (Ph+) metaphases was 36% to 100%, partial cytogenetic response (PCyR) if 1% to 35%, and complete cytogenetic response (CCyR) if 0%. Patients with either CCyR or PCyR were considered to have a major cytogenetic response (MCyR) (≤ 35% Ph + metaphases) 6 …”

Section: Methodsmentioning

confidence: 99%

“…Major molecular response (MMR) was defined as ≤0.1% BCR‐ABL1/ABL1 in the International Scale (IS). Molecular response (MR)4 was defined as BCR‐ABL1/ABL1 transcripts <0.01%, and MR4.5 was defined as BCR‐ABL/ABL1 ≤ 0.0032% IS 4 ) 6,9 …”

Section: Methodsmentioning

confidence: 99%

“…Among patients with CML‐CP, time to response is an important determinant of outcome, 4,5 a fact that is prominently featured in the ELN and other recommendations 6 . However, the clinical impact of early response for patients with de novo accelerated‐phase CML has not yet been evaluated.…”

Section: Introductionmentioning

confidence: 99%

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The clinical impact of time to response in de novo accelerated‐phase chronic myeloid leukemia

et al. 2020

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We aimed to describe the impact of time to response on the outcomes of 75 patients with accelerated‐phase chronic myeloid leukemia (CML‐AP) at diagnosis. Patients had at least 1 feature of AP: blasts ≥15% (n = 2), basophils ≥20% (n = 19), platelets <100 × 109/L (n = 7), cytogenetic clonal evolution (n = 34), or more than one factor (n = 13). Thirty‐three patients received imatinib; 42 received a second‐generation tyrosine kinase inhibitor (2GTKI) (19 dasatinib and 23 nilotinib). We used chi‐square and Kaplan‐Meier analyses to determine the impact of various degrees of molecular and cytogenetic response at early time points (3 and 6 months) on rates of overall cytogenetic and molecular response, overall survival (OS), event‐free survival (EFS), transformation‐free survival (TFS), and failure‐free survival (FFS). After a median follow‐up of 96 months (range: 18‐224 months), the overall rate of complete cytogenetic response was 79%, of major molecular response, 71%, and of molecular reponse (MR)4.5, 59%. Patients who achieved a major cytogenetic response (MCyR) (n = 49) at 3 months had significantly better 3‐year OS (94% vs 75%; P = .002), TFS (98% vs 73%; P < .001), EFS (93% vs 42%; P < .001), and FFS (83% vs 25%; P < .001) rates than patients who did not have MCyR at 3 months. Most (67%) who eventually achieved sustained MR4.5 had achieved MCyR at 3 months. In de novo CML‐AP, early response at 3 and 6 months is a strong determinant of long‐term outcome.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The clinical impact of time to response in de novo accelerated‐phase chronic myeloid leukemia

et al. 2020

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Olverembatinib After Failure of Tyrosine Kinase Inhibitors, Including Ponatinib or Asciminib

Jabbour,

Oehler,

Koller

et al. 2024

JAMA Oncol

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ImportancePatients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) resistant or intolerant to BCR-ABL1 tyrosine kinase inhibitors (TKIs) have limited treatment options. Olverembatinib, which is approved in China, has only been tested in Chinese patients.ObjectiveTo assess the pharmacokinetics, safety, efficacy, and recommended dose of olverembatinib in patients with CML or Philadelphia chromosome–positive ALL resistant or intolerant to at least 2 TKIs.Design, Setting, and ParticipantsThis multicenter phase 1b randomized clinical trial was conducted from January 28, 2020, to January 2, 2024, with a median (range) follow-up of 48 (0-166) weeks. Patients with CML or Philadelphia chromosome–positive ALL were enrolled. This bridging study was performed in part to confirm that there are no racial differences in the pharmacokinetic profile of olverembatinib.InterventionsPatients were randomly assigned to 30, 40, or 50 mg of olverembatinib orally every other day in 28-day cycles.Main Outcomes and MeasuresPharmacokinetic profile of olverembatinib.ResultsOf 80 included patients, 46 (58%) were male, and the median (range) age was 54.0 (21-80) years. The pharmacokinetic profile of olverembatinib was compatible with alternate-day dosing and similar to that in Chinese patients. Based on investigators’ assessments, 60 patients (75%) experienced at least 1 treatment-related adverse event; 32 (40%) experienced grade 3 or higher treatment-related adverse events; and 12 (15%) experienced treatment-related serious adverse events, none of which were fatal. Frequently reported (10% or more) treatment-emergent adverse events included elevated blood creatine phosphokinase (all grades, 31 [39%]; grade 3 or higher, 10 [13%]) and thrombocytopenia (all grades, 23 [29%]; grade 3 or higher, 14 [18%]). Among evaluable patients with chronic-phase CML, complete cytogenetic response (CCyR) occurred in 31 of 51 patients (61%; 95% CI, 46.1-74.2), and major molecular response (MMR) occurred in 25 of 59 patients (42%; 95% CI, 29.6-55.9). Cytogenetic and molecular responses were similar in patients with or without T315I variants. A total of 15 of 26 patients with prior ponatinib treatment (58%; 95% CI, 36.9-76.6) achieved CCyR, and 11 of 30 (37%; 95% CI, 19.9-56.1) achieved MMR. A total of 4 of 8 patients with asciminib resistance (50%; 95% CI, 15.7-84.3) had CCyR, and 4 of 12 (33%; 95% CI, 9.9-65.1) had MMR. The recommended phase 3 dose of olverembatinib is 30 mg every other day in patients without T315I variants.Conclusions and RelevanceIn this trial, olverembatinib had a favorable pharmacokinetic profile, was generally well tolerated, and showed strong antileukemic activity in patients with heavily pretreated chronic-phase CML with or without T315I variants, including prior ponatinib and/or asciminib failure. Olverembatinib may provide a viable new treatment option for patients after failure of 2 or more TKIs.Trial RegistrationClinicalTrials.gov Identifier: NCT04260022

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Hematopoietic Cell Transplantation

Bashir¹,

Shpall²,

Champlin³

2022

Holland‐Frei Cancer Medicine

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Overview Hematopoietic cell transplantation (HCT) is an essential component of therapy for various malignant and nonmalignant conditions and provides the only curative modality for several high‐risk disorders. While HCT can be associated with significant morbidity, meaningful progress has been made to reduce treatment‐related toxicities and improve patient outcomes following HCT. Together with the development of international donor registries and the feasibility of alternative donor transplants, these advances have broadened the indications of HCT in recent years.

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European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

Cited by 1,101 publications

References 137 publications

The clinical impact of time to response in de novo accelerated‐phase chronic myeloid leukemia

The clinical impact of time to response in de novo accelerated‐phase chronic myeloid leukemia

Olverembatinib After Failure of Tyrosine Kinase Inhibitors, Including Ponatinib or Asciminib

Hematopoietic Cell Transplantation

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