Efficacy of mitoxantrone-based salvage therapies in relapsed or refractory acute myeloid leukemia in the Mayo Clinic Cancer Center: Analysis of survival after ‘CLAG-M’ vs. ‘MEC’

Scheckel, Caleb; Meyer, Megan; Betcher, Jeffrey; Al‐Kali, Aref; Foran, James M.; Palmer, Jeanne

doi:10.1016/j.leukres.2020.106300

Cited by 11 publications

(3 citation statements)

References 18 publications

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“…Therefore, we opted for a CLAG-M regimen characterized by less toxicity and a more multidirectional profile of effectiveness that may overcome the challenges arising from the complex pathogenesis of MPAL without the potential selection of any subclones. To date, the CLAG-M protocol has been widely reported to be beneficial in AML with poor prognosis, but has also proven to be well-tolerated ( 17 , 34 – 36 ).…”

Section: Discussionmentioning

confidence: 99%

A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience

Karasek,

Armatys,

Skarupski

et al. 2024

Front. Oncol.

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IntroductionMixed-phenotype acute leukemia (MPAL) is a rare disease with poor prognosis. So far, no standard approach has been established as the “know-how” of MPAL is based only on retrospective analyses performed on small groups of patients.Materials and methodsIn this study, a retrospective analysis of the outcomes of adult MPAL patients included in the PALG registry between 2005 and 2024 who received the CLAG-M hybrid protocol as induction or salvage therapy was performed.ResultsSixteen of 98 MPAL patients received CLAG-M: eight as first-line and eight as salvage therapy. In the first line, two patients achieved partial response (PR), and six achieved complete remission (CR), of whom four successfully underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). Two patients who did not undergo alloHSCT promptly relapsed. Within the whole group, the overall response rate (ORR) was 75% (n = 12/16). With the median follow-up of 13 months, six out of eight patients remain in CR, however, two of them died due to acute graft versus host disease. Out of eight patients who received CLAG-M in the second line, four patients (50%) obtained CR. AlloHSCT was conducted in seven cases, six of which were in CR. Only two patients remained in CR at the time of the last follow-up. Tolerance to treatment was good. The median times for severe neutropenia and thrombocytopenia were 22 days (range, 16–24) and 17 days (range, 12–24), respectively. Overall, grade 3-4 infections were observed in 12 cases, and all infections presented successful outcomes.ConclusionsCLAG-M is an effective first-line salvage regimen for MPAL with an acceptable safety profile. Early achievement of CR with prompt alloHSCT allows for satisfactory disease control.

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Section: Discussionmentioning

confidence: 99%

A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience

Karasek,

Armatys,

Skarupski

et al. 2024

Front. Oncol.

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“…According to reported studies, the addition of medications with different mechanisms to CLAG can increase the efficacy for R/R AML. CLAG regimens plus “X” includes mitoxantrone (M) [ 2 , 6 ], pegylated liposomal doxorubicin [ 7 ], or aclacinomycin [ 8 ], most of which are cytotoxic agents. The CR rates due to the above regimens range from 49 to 75%, which is comparable to the CLAG regimen.…”

Section: Introductionmentioning

confidence: 99%

Decitabine as epigenetic priming with CLAG induce improved outcome of relapsed or refractory acute myeloid leukemia in children

Zhang,

Li,

Wang

et al. 2024

Clin Epigenet

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Background Decitabine (DAC), a DNA methyltransferase inhibitor, has shown efficacy combined with chemotherapy for relapsed or refractory (R/R) acute myeloid leukemia (AML) in adults, but less is known about its efficacy in children. Accordingly, we conducted a study which involved a priming regimen consisting of DAC with cladribine, cytarabine, and granulocyte-stimulating factor (DAC-CLAG) and compared the efficacy and safety of this regimen with CLAG alone. Methods A total of 39 R/R AML children who received the CLAG or DAC-CLAG regimen in Shanghai Children’s Hospital were retrospectively enrolled in this non-randomized study. These regimens were studied sequentially over time. Twenty-two patients received CLAG from 2015, while 17 patients were administered epigenetic priming with DAC before CLAG from 2020. Patients were subsequently bridged to stem cell transplantation (SCT) or consolidation chemotherapy. Complete remission (CR) and adverse effects were analyzed by Fisher’s exact test, and survival was analyzed by the Kaplan–Meier method. Results DAC-CLAG conferred a numerically higher CR compared to CLAG (70.59% vs 63.64%; P = 0.740). High CR rates occurred in patients with good cytogenetics (P = 0.029) and prior induction without cladribine (P = 0.099). The 1-year event-free survival (EFS) was 64.71% ± 11.59% and 63.31% ± 10.35% in the DAC-CLAG and CLAG group (P = 0.595), and 1-year overall survival (OS) was 81.45% ± 9.72% and 77.01% ± 9.04%, respectively (P = 0.265). The 1-year OS and EFS after SCT were higher in the DAC-CLAG than in the CLAG cohort (100% vs 92.31% ± 7.39%, P = 0.072; 92.31% ± 7.39% vs 85.71% ± 9.35%, P = 0.158). Univariate analysis revealed that a good prognosis included good cytogenetics (P = 0.002), non-complex karyotype (P = 0.056), CR on reinduction (P < 0.0001), and bridging to SCT (P = 0.0007). Use of a hypomethylating agent (P = 0.049) and bridging to SCT (P = 0.011) were independent prognostic factors. Grade 3/4 hematologic toxicity and infection were the main adverse events. Conclusions DAC prior to the CLAG regimen improved remission in pediatric R/R AML, and was feasible and well tolerated. CLAG ± DAC as a salvage therapy prior to SCT induced improved survival.

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“… 1 , 2 CLAG-M (cladribine, high-dose cytarabine, granulocyte–colony-stimulating factor/filgrastim, and mitoxantrone) is a contemporary (re)induction chemotherapy regimen with encouraging response rates and clinical outcomes. 3 , 4 , 5 , 6 , 7 However, because of the inclusion of cladribine and use of higher doses of cytarabine, CLAG-M is associated with increased myelosuppression, which may result in a higher risk of infection. 8 …”

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confidence: 99%

Invasive fungal infections after CLAG-M/CLAG chemotherapy for acute myeloid leukemia and high-grade myeloid neoplasms

et al. 2023

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CLAG-M (cladribine, high-dose cytarabine [HiDAC], G-CSF, mitoxantrone)/CLAG are contemporary intensive chemotherapy regimens associated with higher and deeper complete remission rates than 7+3 (cytarabine, anthracycline)/HiDAC, but with greater myelosuppression and potential infection risks. Here, we compared the cumulative incidence (CI) and patterns of invasive fungal disease (IFD) between these regimens by identifying proven/probable and possible cases of IFD following CLAG-M (n=332) and 7+3 (n=115) chemotherapy and subsequent treatment cycles in adults ≥18 years old with newly diagnosed (ND) or relapsed/refractory (R/R) AML or other high-grade myeloid neoplasms between 2006 and 2018. By 90 days (D90) after initiating treatment, the CI of proven/probable IFD was 20% with CLAG-M and 12% with 7+3 (p=0.17). There was no significant difference in the CI of IFD between ND CLAG-M and R/R CLAG-M. Without mold-active prophylaxis, the D90 CI of proven/probable IFD was significantly higher in the CLAG-M than the 7+3 cohort (28% versus 11%; p=0.007), but this difference was mitigated with mold-active prophylaxis (CLAG-M, 7.5%; 7+3, 0%; p=0.65). After each chemotherapy treatment cycle, the CI of newly diagnosed IFD was similar, ranging from 15-20%. Use of mold-active prophylaxis was the only factor associated with reduced IFD risk in adjusted models (HR, 0.32; 95% confidence interval, 0.18-0.56). Together, these data indicate that the IFD risk with CLAG-M is higher than with 7+3 in the absence of mold-active prophylaxis; use of mold-active prophylaxis mitigates this risk.

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Efficacy of mitoxantrone-based salvage therapies in relapsed or refractory acute myeloid leukemia in the Mayo Clinic Cancer Center: Analysis of survival after ‘CLAG-M’ vs. ‘MEC’

Cited by 11 publications

References 18 publications

A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience

A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience

Decitabine as epigenetic priming with CLAG induce improved outcome of relapsed or refractory acute myeloid leukemia in children

Invasive fungal infections after CLAG-M/CLAG chemotherapy for acute myeloid leukemia and high-grade myeloid neoplasms

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