Successful Treatment of Acute Myeloid Leukemia with CPX-351 in 2 Patients in the United Kingdom during the COVID-19 Pandemic
Authors: Munisamy Sreetharan , Choudhuri Satarupa 
Published: November 2021

Introduction: The COVID-19 pandemic hit the United Kingdom in early 2020. High infection rates prompted concern for immunocompromised patients, including patients with AML receiving intensive chemotherapy. CPX-351 (Europe: Vyxeos ® Liposomal; US: Vyxeos ®), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved for the treatment of newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults in Europe and in adults and pediatric patients aged ≥1 year in the United States. Despite concerns about intensive chemotherapy-related myelosuppression, the National Cancer Research Institute AML Working Group recommends that CPX-351 should continue to be administered in patients with adverse-risk cytogenetics and/or secondary AML during the pandemic. We report 2 patients with AML who were successfully treated with CPX-351 in the United Kingdom during the COVID-19 pandemic.

Methods: The patients were diagnosed and managed per institutional guidelines. Two patients received CPX-351 induction (daunorubicin 44 mg/m 2 + cytarabine 100 mg/m 2) on Days 1, 3, and 5 (Days 1 and 3 for second induction) and CPX-351 consolidation (daunorubicin 29 mg/m 2 + cytarabine 65 mg/m 2) on Days 1 and 3, all by 90-minute IV infusion, during the pandemic.

Results: The first patient was a 67-year-old male who presented with generalized fatigue in June 2020 with comorbidities of type 2 diabetes, diabetic nephropathy, and leg ulcers. Blood counts demonstrated a hemoglobin count of 79 g/L, white blood cell count of 0.7×10 9, platelet count of 58×10 9/L, and neutrophil count of 0.2×10 9/L. A bone marrow biopsy revealed AML-MRC with 40% blasts, and the patient had wild-type FLT3, NPM1, and SRSF2. The patient achieved morphologic and cytogenetic remission after 2 CPX-351 induction cycles. The patient then received 1 CPX-351 consolidation cycle but was not a candidate for transplant due to diabetic nephropathy. Tolerability improved with each cycle; the patient experienced neutropenic sepsis during the first induction, a flare up of leg ulcers and cellulitis during the second induction, and no tolerability concerns during the consolidation cycle. After the first induction, recovery of neutrophils and platelets occurred around Day 35 and Day 28, respectively (Figure 1), and counts recovered more quickly with each cycle. This patient was managed without contracting COVID-19 or experiencing any pandemic-related complications.

The second patient was a 69-year-old female who presented with pancytopenia in February 2020 with no significant past medical or drug history. Her hemoglobin count was 66 g/L, white blood cell count was 0.6×10 9/L, platelet count was 17×10 9/L, and neutrophil count was 0.3×10 9/L. The patient was diagnosed with AML-MRC with mutated NPM1, SRSF2, IDH2, and JA2. During the first CPX-351 induction cycle, the patient contracted COVID-19. Some symptoms were present, but the patient did not become significantly unwell from COVID-19. Despite count recovery, the patient remained positive by nasal/oral PCR swab test for several weeks, delaying the delivery of the second CPX-351 induction cycle. After the second CPX-351 cycle began, the patient once again became positive for COVID-19 by PCR swab. The patient remained positive for longer than the first infection but was largely asymptomatic during the cycle (apart from a bout of sepsis). After a period of approximately 3 months from the previous CPX-351 cycle, the patient received a CPX-351 consolidation cycle and achieved complete remission with no measurable residual disease by NPM1 mutation in the bone marrow (Figure 2). The patient was eligible for transplant but declined.

Conclusions: Two patients with AML-MRC were successfully treated with CPX-351 during the COVID-19 pandemic, despite one of the patients contracting and variably testing positive for the disease. During the pandemic, it is important to weigh the benefits of treating AML with curative intent versus the risks of immunosuppression and potential COVID-19 infection. Individualized decisions must be made for each patient based on disease, treatment, and COVID-19 risk factors through discussion with a multidisciplinary team. Although treating patients with AML with CPX-351 during the pandemic can be challenging, it remains an option for appropriate patients with newly diagnosed t-AML or AML-MRC.

Figure 1 Figure 1.

Disclosures

Munisamy: Roche: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau. Choudhuri: AstraZeneca, Bristol-Myers Squibb, Jazz Pharmaceuticals, and Pfizer: Consultancy.