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Rituximab Maintenance Adds No Benefit for Patients With Diffuse Large B-Cell Lymphoma


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After treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), rituximab maintenance therapy seems to provide no additional benefit for patients with diffuse large B-cell lymphoma (DLBCL) in first complete remission, according to data from a phase III trial.1

When added to CHOP, rituximab has been shown to improve long-term overall survival in advanced-stage DLBCL,2 but a U.S. Intergroup study showed that maintenance rituximab added no benefit if rituximab was given with CHOP initially.3 Based on these data, the investigators concluded that the optimal rituximab dose and schedule are not known.


I would say at this point in time, exploring different schedules of rituximab administration in DLBCL seems to be of limited utility.
— Daniel Persky, MD

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Data from a second randomization for rituximab maintenance therapy were reported at the 2019 ASCO Annual Meeting by Pieternella J. Lugtenburg, MD, PhD, of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues.1 The study was later discussed at the Best of ASCO Austin by Daniel Persky, MD, of the University of Arizona Cancer Center, along with other top selected abstracts in lymphoma and chronic lymphocytic lymphoma.4 “These study results corroborated the results of the U.S. Intergroup trial,” said Dr. Persky.

First Randomization: No Benefit to Rituximab Intensification

Dr. Lugtenburg and colleagues previously sought to determine whether intensification of rituximab during the first four cycles of R-CHOP might improve outcomes in patients with DLBCL compared with standard R-CHOP.5 Nearly 600 patients with stage II to IV DLBCL were randomly assigned to receive either R-CHOP14 or an experimental arm consisting of R-CHOP14 and additional intravenous rituximab at 375 mg/m2 on day 8 of the first four cycles. Younger patients (aged 18–65) received eight CHOP14 cycles, whereas older patients (aged 66–80) received six cycles; both groups received eight cycles of induction rituximab. Response was evaluated using positron-emission tomography–computed tomography (PET-CT) scans.

Pieternella J. Lugtenburg, MD, PhD

Pieternella J. Lugtenburg, MD, PhD

They observed that rituximab intensification was not more effective than standard R-CHOP, with similar rates of complete remission and progression-free survival after induction. “These results showed no benefit to more rituximab in ‘induction,’ meaning during CHOP, with equivalent 5-year progression-free survival rates,” Dr. Persky noted.

No Disease-Free Survival Benefit

At second randomization, patients in complete remission were assigned to receive either intravenous rituximab maintenance at 375 mg/m2 every 8 weeks (n = 199) or observation (n = 199) for 2 years, for a total of 12 doses.

The median age of patients was 65 years, and about half were 66 or older. CT scans were performed at 6, 12, 18, and 24 months in both arms. The primary endpoint was disease-free survival from second randomization, and secondary endpoints included overall survival and toxicity.

After a median follow-up of 79.9 months, the 5-year disease-free survival rate was 79% with rituximab maintenance vs 74% with observation. This difference was not statistically significant, with a hazard ratio of 0.83.

Rituximab Maintenance

  • After treatment with R-CHOP, maintenance therapy with rituximab resulted in no additional benefit for patients with DLBCL, corroborating previously published research.
  • Further exploration of different schedules of rituximab administration in DLBCL may prove to be of limited utility.

The secondary endpoint of overall survival was also not significantly different: 85% with rituximab vs 83% with maintenance at 5 years. Subgroup analysis revealed that no clinical subgroup benefited from rituximab maintenance, the investigators reported.

The majority of patients (81%) received all 12 doses of rituximab. “Toxicities were mild, in line with what we would expect with rituximab maintenance,” Dr. Persky added. Infection was the most frequent adverse event, and grade 3 infections occurred in 6% of patients.

“I would say at this point in time, exploring different schedules of rituximab administration in DLBCL seems to be of limited utility,” said Dr. Persky. “The main problem is actually [identifying] a more effective first-line regimen for higher-risk DLBCL and for high-grade B-cell lymphoma.” 

DISCLOSURE: Dr. Lugtenburg has received honoraria/served on advisory board for Celgene, Genmab, Roche, Servier, and Takeda; and has received research funding from Roche, Servier, and Takeda. Dr. Persky has served as a member of an independent data and monitoring committee for MorphoSys and Debiopharm and has served on the advisory board for Bayer.

REFERENCES

1. Lugtenburg EJ, Brown P, van der Holt B, et al: Rituximab maintenance for patients with diffuse large B-cell lymphoma in first complete remission: Results from a randomized HOVON-Nordic Lymphoma Group phase III study. 2019 ASCO Annual Meeting. Abstract 7507. Presented June 4, 2019.

2. Coiffier B, Lepage E, Briere J, et al: CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235-242, 2002.

3. Habermann TM, Weller EA, Morrison VA, et al: Rituximab-CHOP vs CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 24:3121-3127, 2006.

4. Persky DO: Hematologic malignancies: Lymphoma and chronic lymphocytic leukemia. 2019 Best of ASCO Austin. Presented July 26, 2019.

5. Lugtenburg PJ, de Nully Brown P, van der Holt B, et al: Randomized phase III study on the effect of early intensification of rituximab in combination with 2-weekly CHOP chemotherapy followed by rituximab or no maintenance in patients with diffuse large B-cell lymphoma: Results from a HOVON-Nordic Lymphoma Group study. 2016 ASCO Annual Meeting. Abstract 7504. Presented June 5, 2016.


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