Pegylated Liposomal Doxobubicin (PLD) Can Be Escalated in a Dose-Dense, 14 Day CDOP-Rituximab Regimen without Affecting Relative Dose Intensity (RDI) in Patients with Diffuse Large B Cell Lymphoma (DLBCL) Who Are Elderly or Have Compromised Cardiac Status.
Authors: Noga Stephen J , Bosley Judy , Nickoles Pamela , Kumar Pallavi , Monfred Erica 
Published: October 2019

Abstract 2692

Poster Board II-668

Anthracycline/rituximab based chemotherapy such as CHOP-R has become the standard of care for DLBCL where cure is the primary goal. There is a direct correlation between long term survival and the delivery of on time, full dose chemotherapy. Several studies in DLBCL now indicate that this concept of dose intensity may be further exploited by compacting therapy cycles from the usual 21 days to the 14 day “dose dense” regimens. It is hoped that this will result in higher cure rates. Community oncologists often face tough decisions when deciding how to treat the increasing numbers of DLBCL patients who are elderly and have multiple co-morbidities including declining cardiac function and poor performance status (PS). Since PLD has a reported lower cardiac toxicity profile even at higher overall doses than doxorubicin, it was substituted into a dose-dense CHOP-R regimen. Patients >60 years or with left ventricular ejection fractions (LVEF) <45% were enrolled in a phase II dose escalation study of PLD (Doxil*®,20 mg/m2: cohort I, 25 mg/m2: cohort II, 30 mg/m2: cohort III), cyclophosphamide (CY, 750 mg/m2), vincristine (1.4 mg/m2: 2 mg max), prednisone (100 mg PO days 1-5), rituximab (375 mg/m2) on day 1 followed by pegfilgrastim (6 mg, SC) on day 2 of a 14 day cycle. Patients received a planned 6 cycles of chemotherapy or 2 cycles past best response. Safety and SAE's were assessed with each cohort or every 6 patients. Quantitative LVEF was obtained with each cycle, CT's every 3 cycles and PET/CT at baseline and within 60 days of chemotherapy completion. Median age was 76 (62-87) years, 59% were female with baseline LVEF from 12% (with AICD but ECOG PS1) to 75% (PS3). There was no diminution in LVEF for patients receiving >1 cycle of chemotherapy. AE's >grade 2 were neutropenia/fever (n=3), neutropenia (n=1), thrombocytopenia (n=1), chest pain (n=1), hyperglycemia (n=2), CHF (n=1) and worsening pleural effusion (n=1). PPE related to PLD was manageable and minimally delayed therapy. . Patients who were hospitalized (PS >2) or who's PS declined rapidly between study entry and cycle 1 initiation rapidly became too moribund to complete planned therapy.

Escalation of the PLD dose from 20 mg/m2 to 30 mg/m2 did not alter the ability to deliver on time, full dose chemotherapy. Decreasing cycle length to 2 weeks actually increased the RDI to 150% over the standard 3 week regimen. This may be beneficial in the elderly where it is still uncertain if lower survival is due to substandard treatment regimens or a more chemo-resistant NHL phenotype.

In the first 12 evaluable patients completing full course chemotherapy, 10 patients were in CR (CR +nCR), and 1 in PR within 60 days of chemotherapy completion. At 1 year, 6 patients were in CR and 2 had progressive disease. We conclude that CDOP-R 14 warrants further study in the elderly population and in those DLBCL patients with compromised cardiac function.

Disclosures:

Noga: Tibotec, Inc: Honoraria, Research Funding, Speakers Bureau; Amgen, Inc: Honoraria, Speakers Bureau. Off Label Use: Doxil. Substitutes for the standard anthracycline, doxorubicin, in the CHOP regimen for agressive NHL.