|The following article features coverage from the European Hematology Association 2020 virtual meeting. Click here to read more of Hematology Advisor’s conference coverage.|
Inotuzumab ozogamicin (IO) plus rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP) did not improve survival, but was associated with less toxicity, compared with gemcitabine plus R-CVP (G-R-CVP) among patients with previously untreated diffuse large B-cell lymphoma (DLBCL) who were ineligible for standard R-CHOP, according to a phase 2 trial presented at the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.
“In many older comorbid patients, many centers will choose to use an attenuated dose of R-CHOP,” Elizabeth H. Philips, MD, of the University of Manchester and Christie Hospital in the United Kingdom, and lead author and presenter of the study, said. “However, we have very little data on the safety of this regimen for patients who have preexisting cardiac disease —and for those who are unable to use R-CHOP or anthracycline-based chemotherapy, there is currently no standard of care.”
IO is an antibody-drug conjugate that delivers calicheamicin, an anthracycline-like agent, to CD22-positive tumor cells.
This multicenter, phase 2 trial randomly assigned 123 patients with untreated DLBCL to receive R-CVP with either IO or gemcitabine. Patients were pretreated with a corticosteroid, and all patients received 2 cycles of rituximab alone after study treatment. All patients had a reduced cardiac ejection fraction or another comorbidity that was contraindicated to anthracycline use. The primary endpoint was progression-free survival (PFS).
At baseline, the median patient age was 79 years, and comorbidities included 32% who had an ejection fraction 50% or less, 75% with hypertension, 55% with ischemic heart disease, 41% with arrythmia, 38% with renal impairment, 32% with diabetes, and 11% with valvular heart disease.
The objective response rate was higher with IO plus R-CVP at 74.6% compared with 58.3% with gemcitabine plus R-CVP, which was not significant (P =.06).
During a median follow-up of 40 months, there was no significant difference in PFS between arms, with a 2-year rate of 45% with IO plus R-CVP compared with 49% with gemcitabine plus R-CVP (hazard ratio [HR], 0.82; 70% CI, 0.63-1.05; 1-sided P =.21).
However, when adjusted for stratification factors, the PFS HR shifted toward favoring IO (HR, 0.70; 70% CI, 0.54-0.91; 1-sided P =.08). Dr Philips said that this was likely due to an interaction with IPI score. “The main reason for this, we believe, is better treatment delivery for those with high-risk IPI,” she said. The IO arm received a median of 6 cycles, whereas the gemcitabine arm received a median of 4 cycles.
Overall survival (OS), nonrelapse mortality, and disease-specific survival were all similar between arms.
Some grade 3 or higher adverse events (AEs) occurred less frequently with IO compared with gemcitabine, including leukopenia (13% vs 44%), anemia (10% vs 25%), cardiac events (6% vs 21%), and elevated alanine aminotransferase levels (3% vs 17%), respectively. Grade 5 AEs occurred in 14.3% of patients who received gemcitabine compared with 12.7% of patients who received IO.
Dr Philips said, “we demonstrated that IO has a favorable toxicity profile and is associated with higher treatment completion rates and tolerability; therefore, an increased stratified subgroup analysis showed that this regimen was more effective than G-R-CVP for those with a high IPI score.”
Philips E et al. Inotuzumab ozogamicin plus R-CVP is a feasible and effective regimen for frontline treatment of DLBCL in patients who are unfit for R-CHOP: results of a randomised phase 2 UK NCRI trial. Paper Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S136.
This article originally appeared on Cancer Therapy Advisor