Predictors of response to venetoclax plus hypomethylating agent therapy and survival in blastphase myeloproliferative neoplasm

Gangat, Naseema; Ilyas, Rimal; McCullough, Kristen; Begna, Kebede H.; Al‐Kali, Aref; Patnaik, Mrinal M.; Litzow, Mark R.; Mangaonkar, Abhishek A.; Alkhateeb, Hassan B.; Shah, Mithun Vinod; Elliott, Michelle A.; Foran, James M.; Badar, Talha; Palmer, Jeanne; Hanson, Curtis A.; Pardanani, Animesh; Tefferi, Ayalew

doi:10.3324/haematol.2022.282019

Cited by 8 publications

(29 citation statements)

References 17 publications

(35 reference statements)

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“…The current retrospective experience with CPX-351 in patients with MPN-BP was not overtly different than previous observations in similar patients receiving standard 7 + 3 induction or HMA-Ven [4,5]. The observed CR/CRi rates with 7 + 3 induction and HMA-Ven were 35%/24% and 26%/17%, respectively [4,5].…”

Section: Dear Editorcontrasting

confidence: 57%

“…Reported chemotherapeutic regimens for MPN-BP included either intensive acute myeloid leukemia (AML)-like induction chemotherapy with 7(cytarabine)+3(daunorubicin/idarubicin), or less intensive treatment with hypomethylating agent (HMA) based combinations with venetoclax (Ven) or ruxolitinib; associated CR/ CRi rates were 59% (AML-like induction), 43% (HMA-Ven) and 8% (HMA-ruxolitinib) [4][5][6][7]. CPX-351 (Vyxeos™) is a liposomal formulation of daunorubicin and cytarabine and is currently FDAapproved for elderly patients with secondary AML with myelodysplasia related changes and therapy-related AML.…”

Section: Dear Editormentioning

confidence: 99%

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CPX-351 (Vyxeos™) treatment in blast-phase myeloproliferative neoplasm (MPN-BP): real-world experience in 12 consecutive cases

et al. 2023

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Section: Dear Editorcontrasting

confidence: 57%

Section: Dear Editormentioning

confidence: 99%

CPX-351 (Vyxeos™) treatment in blast-phase myeloproliferative neoplasm (MPN-BP): real-world experience in 12 consecutive cases

et al. 2023

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“…24 By contrast, the CR/CRi rate in a retrospective study of 47 patients with MPN-BP treated with Ven-HMA was reported at 43% and was higher than historically documented for HMA alone. 28 Furthermore, 7 of 13 (54%) transplant-eligible patients in CR/CRi, in the particular study, 28 were successfully bridged to ASCT. Unlike the case with Ven-HMA, preliminary reports on the use of CPX-351 in MPN-BP have not been as encouraging.…”

mentioning

confidence: 92%

“…In other words, a prospective controlled study is necessary to clarify the value of pre‐transplant bridging chemotherapy in both MPN‐BP and MPN‐AP. In the meantime, our current choice for pre‐transplant bridging chemotherapy is combination of Ven and HMA and we recommend an individualized approach in its implementation, based on bone marrow/circulating blast burden, likelihood of response, and risk of transplant‐barring complications associated with bridging chemotherapy 28 . Finally, post‐transplant management should include systematic monitoring of molecular or morphologic/clinical relapse and application of pre‐emptive or salvage donor lymphocyte infusions and second allograft in carefully selected patients 41 …”

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confidence: 99%

“…Based on the above‐outlined information, it is reasonable to conclude that conventional chemotherapy is awfully inadequate in securing long‐term survival in MPN‐BP, which, fortunately, appears to be possible with ASCT. Accordingly, recent efforts have focused on less intensive treatment approaches with the goal of attaining CR/CRi, to transition to ASCT, without subjecting patients to complications associated with standard AML‐like induction therapy 28 . In this regard, HMA‐based combinations withVen 28–30 or ruxolitinib 24,31 have been evaluated; in a Myeloproliferative Neoplasms Research Consortium phase‐2 study of 25 patients with MPN‐BP or MPN‐AP, treated with Ven‐ruxolitinib, a CR/CRi rate of only 8.1% was reported 24 .…”

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Blast phase myeloproliferative neoplasm: Transplant to the rescue

Tefferi

Bacigalup

2023

American J Hematol

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Primary myelofibrosis: 2023 update on diagnosis, risk‐stratification, and management

Tefferi

2023

American J Hematol

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Disease Overview Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell‐derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations; additional features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, risk of leukemic progression, and shortened survival. Diagnosis Bone marrow examination with cytogenetic and mutation studies provides integrated diagnostic information; presence of JAK2, CALR or MPL mutation is expected but not required. New Classification System The International Consensus Classification distinguishes “prefibrotic” from “overtly fibrotic” PMF; the former might mimic essential thrombocythemia (ET) in its presentation. Approximately 15% of patients with ET or polycythemia vera (PV) might progress into post‐ET/PV MF. Mutations SRSF2, ASXL1, and U2AF1‐Q157 mutations predict inferior survival in PMF; RAS/CBL mutations predict resistance to ruxolitinib therapy. Type 1/like CALR mutation is associated with superior survival. Karyotype Very high‐risk abnormalities include −7, inv (3), i(17q), +21, +19, 12p‐ and 11q‐. Favorable risk abnormalities include normal karyotype or isolated +9, 13q‐, 20q‐, 1q abnormalities and loss of Y chromosome. Risk Stratification Contemporary prognostic systems include GIPSS (genetically‐inspired prognostic scoring system) and MIPSS70+ version 2.0 (MIPSSv2; mutation‐and karyotype‐enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype; MIPSSv2 includes, in addition, clinical risk factors. Risk‐Adapted Therapy Observation alone is advised for MIPSSv2 “low” and “very low” risk disease (estimated 10‐year survival 56%–92%); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment of choice for “very high” and “high” risk disease (estimated 10‐year survival 0–13%), as well as in carefully selected patients with intermediate‐risk disease (estimated 10‐year survival 30%). Drug therapy in MF is currently palliative and targets anemia, splenomegaly, and constitutional symptoms. JAK2 Inhibitors Ruxolitinib, fedratinib, and pacritinib are FDA approved and respectfully utilized in patients failing treatment with hydroxyurea, ruxolitinib, or with platelet count <50 × 10 (9)/L. Momelotinib is another JAK2 inhibitor that is poised for approval sometime in 2023 and has shown erythropoietic benefits, in addition to affecting spleen and symptom responses. Other Treatment Modalities Splenectomy is considered for drug‐refractory splenomegaly and involved field radiotherapy for non‐hepatosplenic EMH and extremity bone pain. New Directions New agents, alone or in combination with ruxolitinib, are currently under clinical trial investigation (ClinicalTrials.gov) and preliminary results were presented at the 2022 ASH annual meeting and highlighted in the current review.

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Predictors of response to venetoclax plus hypomethylating agent therapy and survival in blastphase myeloproliferative neoplasm

Abstract: Not available.

Cited by 8 publications

References 17 publications

CPX-351 (Vyxeos™) treatment in blast-phase myeloproliferative neoplasm (MPN-BP): real-world experience in 12 consecutive cases

CPX-351 (Vyxeos™) treatment in blast-phase myeloproliferative neoplasm (MPN-BP): real-world experience in 12 consecutive cases

Blast phase myeloproliferative neoplasm: Transplant to the rescue

Primary myelofibrosis: 2023 update on diagnosis, risk‐stratification, and management

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