ASH Annual Meeting and Exposition
ASH Annual Meeting and Exposition
Perspective from Andre Goy, MD, MS
Perspective from David Steensma, MD
December 02, 2018
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Shorter chemotherapy course 'equally effective' in diffuse large B-cell lymphoma

Perspective from Andre Goy, MD, MS
Perspective from David Steensma, MD
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Viola Poeschel, MD
Viola Poeschel

SAN DIEGO — Reducing administration of CHOP chemotherapy by two cycles appeared as effective as the standard six cycles for younger patients with low-risk diffuse large B-cell lymphoma, according to results of the phase 3 FLYER trial presented at ASH Annual Meeting and Exposition.

Six cycles of CHOP chemotherapy — which contains cyclophosphamide, doxorubicin, vincristine and prednisone — plus six courses of rituximab (Rituxan; Genentech, Biogen), or R-CHOP, is the standard of care for young patients aged 18 to 60 years with DLBCL.

Results of the MInT trial — published in 2006 in The Lancet Oncology — established a subgroup of patients with DBLCL with an age-adjusted International Prognostic Index of 0 and no bulky disease who had favorable prognosis.

“As we learned from the MInT trial that there is a patient population with an excellent prognosis, we wanted to investigate whether we could de-escalate therapy in these patients without compromising their prognosis and whether this would also lead to less toxicity,” Viola Poeschel, MD, of Saarland University Medical School in Homburg/Saar, Germany, told HemOnc Today. “We believed that this should be possible and that reducing chemotherapy, and therefore toxicity, would represent a major benefit for patients. Data from the MInT trial were presented for the first time during ASH 2004, and our trial started recruiting in December 2005.”

With the reduced regimen — which includes four cycles of R-CHOP with two additional cycles of rituximab — patients receive 84 days of chemotherapy, compared with 126 days with the standard regimen.

“With a shorter duration of chemotherapy, patients are back to daily life with their families and back to work more quickly,” Poeschel said in a press release. “Our study shows you can spare two cycles of chemotherapy and it is equally effective. We think this will be the new standard treatment for this patient population.”

The analysis included 588 patients aged 18 to 60 years (median age, 48 years) with stage I to stage II DLBCL, 295 of whom received six cycles of R-CHOP and 293 of whom received four cycles of R-CHOP with two additional cycles of rituximab alone.

PFS served as the study’s primary endpoint.

Median follow-up was 66 months.

Researchers found that PFS, EFS and OS appeared as good with the shorter cycle as with the longer treatment cycle.

Ninety-six percent (95% CI, 94-99) of patients assigned the shorter regimen achieved 3-year PFS compared with 94% (95% CI, 91-97) of patients assigned the standard regimen. The difference met noninferiority criteria of the trial.

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Three-year EFS was 89% in both groups, and 3-year OS was 99% (95% CI, 98-100) with the shorter regimen and 98% (95% CI, 96-99) with the longer regimen.

Multivariable analyses showed HRs of 1 (95% CI, 0.7-1.6) for EFS, 0.9 (95% CI, 0.5-1.6) for PFS and 0.8 (95% CI, 0.4-1.9) for OS.

Relapse occurred in 4% (95% CI, 2-7) of patients in the shorter treatment group and 5% (95% CI, 3-8) in the longer treatment group. Although 33% of relapses occurred within the first 2 years, researchers noted they continue to observe relapses with longer follow-up.

“A standard of care is established after a scientific discussion, which will start now,” Poeschel told HemOnc Today. “Our results may contribute so that future therapy guidelines for this patient population might be changed in the way that these patients received four cycles of R-CHOP in 21-day cycles plus two courses of rituximab instead of six 21-day cycles of R-CHOP. As the relapse pattern in both arms were similar, I don’t anticipate any reluctance.”

Researchers observed a reduction in toxicity of about a third in the shorter treatment group —1,295 adverse events occurred among those who underwent six cycles of R-CHOP compared with 835 adverse events among those who underwent four cycles.

The number of documented events of leukocytopenia (any grade, 237 vs. 171; grade 3-4, 110 vs. 80), anemia (any grade, 172 vs. 107; grade 3-4, 8 vs. 2) and thrombocytopenia (any grade, 17 vs. 16; grade 3-4, 7 vs. 5) were higher in the longer treatment group. There also were fewer cases of paresthesia (any grade, 370 vs. 227; grade 3-4, 14 vs. 12), nausea (any grade, 319 vs. 195; grade 3-4, 12 vs. 6), infection (any grade, 156 vs. 98; grade 3-4, 23 vs. 20) and mucositis (any grade, 105 vs. 68; grade 3-4, 3 vs. 1).

Researchers plan to follow the patients for an additional 5 years to determine the effect of the shorter treatment cycle on long-term side effects.

“It would also be very interesting to investigate whether therapy could even be more de-escalated by performing an early PET, for example, after two cycles of R-CHOP, or to investigate whether patients being PET positive after four cycles of R-CHOP would profit from an irradiation after six cycles of R-CHOP,” Poeschel told HemOnc Today. – by Alexandra Todak

References :

Pfreundschuh M, et al. Lancet Oncol. 2006;7:379-391.

Poeschel V, et al. Abstract 781. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.

Disclosures: Poeschel reports travel grants from Amgen and Roche. Please see the abstract for all other authors’ relevant financial disclosures.