Blood cancers

Modified chemo regimen less toxic for transplant-ineligible lymphoma patients

A pared back three-drug salvage regimen for patients with relapsed-refractory diffuse large B-cell lymphoma (RR-DLBCL) who are ineligible for stem cell transplant provides outcomes ‘as good’ as a widely used four-drug regimen but with the benefit of reduced toxicity, according to an Australian study.

Investigators from NSW, Victoria and Canberra who conducted the multicentre phase II trial of the R-IE regimen in 30 patients say it is a good alternative for older patients with RR-DLBCL who are considered unsuitable for high-dose chemotherapy because of comorbidities and impaired performance data.

Professor Mark Hertzberg from the Department of Haematology at Prince of Wales Hospital in Sydney and an investigator on the study told the limbic the trial was designed to reduce the toxicity while maintaining ‘reasonable efficacy’ of a standard regimen used widely in patients with relapsed refractory disease. 

“There are about three standard regimens around the world for transplant ineligible patients and we chose to modify the most common one used in Australia and North America,” he said referring to the R-ICE regimen, which combines rituximab with ifosfamide, carboplatin, and etoposide.

“We decided to drop the carboplatin, which has got nephrotoxicity and myelotoxicity. We then reduced the ifosfamide and etoposide doses by 20% and incorporated rituximab into that.”

The study is unique says Professor Hertzberg who points out that enrolled patients were much older than patients in most other salvage regimen studies. The median age of patients was 76 years – the oldest patient was 84.

Patients were administered rituximab 375 mg/m2 day one, ifosfamide 1333mg/m2 days one to three, and etoposide 80mg/m2 days 1 to 3 every 21 days for six cycles plus two doses of rituximab.

The overall response rate (ORR) was 76%, with 55% achieving complete response (CR). The median progression free and overall survival was 23 months and 24 months, respectively.

According toProfessor Hertzberg the outpatient R-IE regimen was well tolerated with only six episodes of febrile neutropenia requiring hospital admission, and grade 3–4 neutropenia in 27% and 3% of patients, respectively.

Not all patients completed the entire planned treatment; six patients stopped treatment early due to haematological toxicity and/or infection, five patients experienced cycle delays, while four had progressive disease.

By comparison, Professsor Hertzberg said multiple episodes of cycle delays due to haematological toxicity and much higher non-completion rates are common with the standard care R-ICE regimen

“In era where there is no good standard care, R-IE is at least as safe and at least as effective as the other standard care regimens and its associated with less toxicity in a group that have a very poor prognosis,” said Professor Hertzberg of the findings.

He did however note a number of caveats.

“We had fewer patients relapsing within 12 months – about 23% of our patients had early relapse where normally you would expect closer to half. So the majority of our patients relapsed more than 12 months after initial treatment and that may well account for the improved complete response rate.”

He also noted that 40% of patients were rituximab naïve because rituximab was not reimbursed in Australia at the time the study was carried out and this group appeared to have more favourable response rates and survival outcomes than those who had received prior rituximab. Although there was no statistically significant difference between the two cohorts, he added.

“The more aggressive therapies like RHAP of RGDP would be for patients who are transplant eligible – currently up to the age of 65 and probably up to the age of 70 if they’re fit.

But for patients either over the age of 70 or unfit with co-morbidities or poor performance data then you would need to use one of the less toxic regimens like this one.”

The study is published in Luekemia & Lymphoma

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