Dose-Adjusted Intensive Chemotherapy Is Safe and Tolerable in Older Patients with Ph-Negative ACUTE Lymphoblastic Leukemia

Abstract

Topic Significance & Study Purpose/Background/Rationale Outcomes of older adults with acute lymphoblastic leukemia (ALL) remain poor [PMID 19897583, 28419558, 22409379, 10653870]. PEG-Asparaginase (PEG-Asp) is a key component of the chemotherapeutic regimens for treatment of pediatric and younger adult ALL [PMID 29450465]. Older patients with Ph-negative ALL are often not offered PEG-Asp containing regimen due to concerns related to tolerability and safety [PMID 28355969]. Methods, Intervention, & Analysis The Adult Leukemia Program at Mount Sinai Hospital developed an age-based, dose-adjusted pediatric chemotherapy regimen for adults (≥40 years) with diagnosis of Ph-negative ALL. For patients up to 60 years, prednisone (PRD) dose was reduced to 40 mg/m2/day, and PEG-Asp to 1000 units/m2. For patients aged ≥61 years, PRD was further reduced to 25 mg/m2/day. A PEG-Asp oriented supportive care plan was developed to prevent and treat Asp-related adverse effects (AE) based on Antithrombin III (ATIII) and fibrinogen levels. Findings & Interpretation Fourteen patients with median age 60 years (45 – 76) were evaluable, and three patients were ≥ 70 years. Eleven patients had significant co-morbidities at diagnosis, including diabetes, hypertension, previous history of cancer, coronary artery disease, obesity, alcohol related chronic pancreatitis, and chronic diarrhea. Eleven patients (79%) attained a complete remission (CR) at the end of induction (EOI), four of them with detectable minimal residual disease (MRD). Five patients underwent allogeneic hematopoietic stem cell transplantation (HCT) while in CR (age range 46 – 60), four remain in CR at last follow up (median 563 days, range 259 – 883), and one died of relapsed disease 67 days post-HCT. The other eight patients who are receiving chemotherapy are in remission at last follow up (median 317 days, range 63 – 714). Observed PEG-Asp related AE were asymptomatic hypofibrinogenemia and low ATIII levels (n=10), severe hyperbilirubinemia (n=1), and non-life-threatening venous thrombosis (n=1). No patient experienced early death, severe allergic reaction or clinical pancreatitis. Discussion & Implications This dose-adjusted PEG-Asp containing regimen was associated with an encouraging CR rate and with tolerable and manageable AE in this patient population with significant co-morbidities. Treatment related mortality was 0%. Twelve of the 14 patients are currently in sustained remission (median follow-up 399 days, range 63-883). Further prospective evaluation is under way.