Acute myeloid leukemia after age 70 years: A retrospective comparison of survival following treatment with intensive versus <scp>HMA</scp> ± venetoclax chemotherapy

Begna, Kebede H.; Gangat, Naseema; Al‐Kali, Aref; Litzow, Mark R.; Patnaik, Mrinal M.; Pardanani, Animesh; Hook, C. Christopher; Wolanskyj, Alexandra P.; Hanson, Curtis A.; Ketterling, Rhett P.; Tefferi, Ayalew

doi:10.1002/ajh.26112

Cited by 8 publications

(9 citation statements)

References 7 publications

(20 reference statements)

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“…Among patients who received HMA in the frontline, they observed CR/CRi rates of 32% and a 3‐year OS of 10%. Conversely, among patients who received intensive chemotherapy, they observed CR/CRi rates of 62% and 3‐year OS of 23%, concluding that intensive chemotherapy may be superior in achieving long‐term survival 45 . However, responses rates and long‐term OS in our study using DNT compare favorably with these data and may provide similar benefit with less incidence of toxicity in this older population.…”

Section: Discussionsupporting

confidence: 40%

Long‐term results of low‐intensity chemotherapy with clofarabine or cladribine combined with low‐dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia

et al. 2021

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The treatment of older patients with newly diagnosed acute myeloid leukemia (AML) using intensive chemotherapy is associated with treatment intolerance and poor survival. We evaluated two new lower-intensity regimens with clofarabine (n = 119) or cladribine (n = 129) combined with low-dose cytarabine (LDAC) alternating with decitabine. We reviewed response rates by subgroup and long term outcomes of 248 patients with newly diagnosed non core-binding-factor AML treated on two clinical trials investigating double nucleoside-analogue therapy (DNT) alternating with HMA from October, 2008 to April, 2018. Of 248 patients with a median age of 69 years (range, 49-85 years), 102 patients (41%) were ≥ 70 years, and 108 (44%) had adverse karyotype. Overall, 164 patients (66%) responded: 147 (59%) complete remission (CR) and 17 (7%) CR with incomplete count recovery (CRi). With a median follow up of 60 months, median relapse-free and overall survival (OS) were 10.8 and 12.5 months, respectively. The 2-year OS was 29%. Among patients with normal karyotype, the CR/CRi rate was 79% and the median OS 19.9 months. High response rates and OS were observed in patients with mutations in NPM1, FLT3, IDH2, and RUNX1. The 4-and 8-week mortality rates were 2% and 11%, respectively. The backbone of clofarabine or cladribine and LDAC alternating with decitabine was effective and safe for the treatment of older patients with newly diagnosed AML. Incorporating targeted therapies could extend the efficacy of this approach and provide more curative therapeutic options in this AML population.

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Section: Discussionsupporting

confidence: 40%

Long‐term results of low‐intensity chemotherapy with clofarabine or cladribine combined with low‐dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia

et al. 2021

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“…Indeed, although the trial of DiNardo et al reported a median overall survival of 14.7 months (95% CI 11.9-18.7), real-world studies showed substantially lower survival. With the only exception of Cherry et al and Mirgh et al, which reported a median survival of more than 15 months, the other authors showed an overall survival ranging between 4 and 13 months [21,24,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. As a consequence, the pooled median survival in our meta-analysis was 9.37 months (95% CI 8.81-10.5), significantly lower than that reported by DiNardo et al This difference was also confirmed in the secondary analyses that we performed, in particular after we excluded studies enrolling subjects with worse prognoses (i.e., secondary, therapy-related, and TP53mutated AML).…”

Section: Discussionmentioning

confidence: 98%

Venetoclax with Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Survival Data from Real-World Studies

Ucciero,

Pagnoni,

Scotti

et al. 2023

Cancers

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In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) who were unfit for intensive chemotherapy and became the standard of care after the publication of the pivotal RCT VIALE-A. However, it is still not clear to what extent the results observed in the VIALE-A apply to a real-world setting. For this reason, we carried out a systematic review and meta-analysis of real-world studies on newly diagnosed patients with AML, ineligible for intensive induction chemotherapy, receiving first-line VEN+HMA. We then compared their results in term of survival with those from the VIALE-A. Kaplan-Meier curves were extracted from all included studies and individual survival data was reconstructed. We then estimated a pooled survival curve and compared it with the results of the VIALE-A using the log-rank test. We also conducted a secondary analysis including only studies considering VEN plus azacytidine (AZA) as treatment, as this was the schedule originally used in the VIALE-A. Nineteen real-world studies met the inclusion criteria and were included in the systematic review. Most of them reported a worse survival than the VIALE-A. The pooled survival curve was similar to that reported in the VIALE-A during the first three months of treatment but diverged thereafter (p-value = 0.0001). The pooled median survival among the real-world studies was 9.37 months (95%CI 8.81–10.5), substantially lower than that reported in the VIALE-A (14.7 months; 95%CI 11.9–18.7). Results slightly increased when the analysis was restricted to the studies using VEN+AZA as treatment (median survival: 11.5 months; 95%CI 10.2–14.8). Survival of newly diagnosed AML patients treated with VEN+HMAs in a real-world setting seems to be lower than previously reported in the VIALE-A, while the effect of VEN+AZA is more in line with expected results. Future studies are needed to evaluate whether this apparent discrepancy is due to the different characteristics of enrolled patients or to a non-optimal adherence to therapy, and whether alternative regimens can provide better results in terms of safety and effectiveness.

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“…The above‐outlined observations suggested the apparently crucial role of AHSCT in securing long‐term survival in MPN‐BP as well as the favorable short‐term survival impact of chemotherapy‐induced CR/CRi. Our recently published experience in AML patients above age 70 years was similar in confirming the survival advantage for intensive chemotherapy, for otherwise fit patients, and the value of HMA‐based therapy for prolonging short‐term survival in patients not considered fit to receive AML‐like induction chemotherapy 3 . The majority of patients with MPN‐BP are older than age 65 years and often suffer from comorbidities that make them ineligible for intensive chemotherapy 2 .…”

Section: Introductionmentioning

confidence: 73%

Venetoclax with azacitidine or decitabine in blast‐phase myeloproliferative neoplasm: A multicenter series of 32 consecutive cases

et al. 2021

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Venetoclax (Ven) combined with a hypomethylating agent (HMA) has now emerged as an effective treatment regimen for acute myeloid leukemia, in both de novo and relapsed/refractory setting. The current multicenter study retrospectively examined Ven + HMA treatment outcome among 32 patients (median age 69 years; 59% males) with blast‐phase myeloproliferative neoplasm (MPN‐BP). Pre‐leukemic phenotype included essential thrombocythemia (ET)/post‐ET myelofibrosis (34%), polycythemia vera (PV)/post‐PV myelofibrosis (38%) and primary myelofibrosis (28%). Twenty‐nine study patients were fully annotated cytogenetically and molecularly (NGS): 69% harbored complex karyotype and/or mutations, including TP53 (41%), IDH1/2 (21%), ASXL1 (21%), N/KRAS (14%), SRSF2 (10%), EZH2 (10%) and U2AF1 (7%). All patients received Ven combined with either azacitidine (n = 12) or decitabine (n = 20); either up front (n = 23) or after failing another induction therapy (n = 9). Complete remission with (CR) or without (CRi) count recovery was achieved in 14 (44%) patients and was more likely to occur in the absence of pre‐leukemic PV/post‐PV myelofibrosis phenotype (p < .01), complex karyotype (p < .01) or K/NRAS (p = .03) mutations; seven of eight patients (88%) without vs four of 21 (19%) with complex karyotype or K/NRAS mutation achieved CR/CRi (p < .01); all 11 informative patients with pre‐leukemic PV/post‐PV myelofibrosis phenotype displayed complex karyotype (p < .01). In contrast, neither TP53 (p = .45) nor IDH1/2 (p = .63) mutations affected response. Compared to historical controls treated with HMA alone (n = 26), the CR/CRi rate (44% vs 4%) and median survival (8 vs 5.5 months) were more favorable with Ven + HMA, but without significant difference in overall survival. Importantly, six patients with CR/CRi subsequently received allogeneic hematopoietic stem cell transplant (AHSCT). Note, Ven + HMA produces robust CR/CRi rates in MPN‐BP, especially in the absence of RAS mutations and complex karyotype, thus enabling AHSCT, in some patients.

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Acute myeloid leukemia after age 70 years: A retrospective comparison of survival following treatment with intensive versus HMA ± venetoclax chemotherapy

Cited by 8 publications

References 7 publications

Long‐term results of low‐intensity chemotherapy with clofarabine or cladribine combined with low‐dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia

Long‐term results of low‐intensity chemotherapy with clofarabine or cladribine combined with low‐dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia

Venetoclax with Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Survival Data from Real-World Studies

Venetoclax with azacitidine or decitabine in blast‐phase myeloproliferative neoplasm: A multicenter series of 32 consecutive cases

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