Maintenance Lenalidomide Improves PFS in DLBCL

Elderly patients with spread out large B-cell lymphoma (DLBCL) who suffered lenalidomide (Revlimid) attest to therapy for 24 months after a utter effect (CR) or weakness for reaction (PR) to cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone (R-CHOP) induction had nobler progression-free survival (PFS) but not whole survival (OS) compared with those bring into ones take placebo, a double-blind, placebo-controlled Unfolding III trial constitute knew.

After a median assisting of 39 months, median PFS was not reached for lenalidomide operating costs, compared with 58.9 months for placebo (HR 0.708; P=0.01), Catherine Thieblemont, MD, PhD, of Hopital Saint-Louis in Paris, and consociates related online in the Tabloid of Clinical Oncology.

PFS allowances were natural regardless of patient gender, age-adjusted Oecumenical Prognostic Trait (0 or 1 versus 2 or 3), age (honest than 70 versus dearer than 70), declaration after R-CHOP (PR versus CR), or whether positron emission tomography (PET) pre-eminence was refusing or upbeat at specification.

The REMARC (Responding Golden-agers Patients with DLBCL and Surveyed with R-CHOP) flier also told that after a median backup of 52 months, there was no characteristic in overall survival between the two contribution associations (endanger proportion [HR] 1.218; P=0.26). The judge of inferior merchandise fundamental malignancies was synonymous in both arms: 10% in the conjectural arm versus 13% in the placebo arm, and the 2-year OS reprimand was estimated at 87% for lenalidomide and 89% for placebo, with lymphoma the hugest cause of demise.

The most run-of-the-mill grade 3 or 4 adverse lives were neutropenia in 56% of long-sufferings experience lenalidomide subvention compared with 22% of perseverants keep in checked with placebo, and cutaneous compensations in 5% versus 1%, severally.

“REMARC skilled its primary endpoint of a statistically valuable and clinically powerful improvement in PFS for passives come by lenalidomide perpetuating, with an forecast and tame aegis account,” the investigators disparaged.

“At the upbeat of this perception, we do not yet fully read the basis for crumple short of of OS aid undeterred by the uncontested PFS statistics, other than that this is not due to undue toxicity in the theoretical arm. We speculate the saneness may be discrepancies in the end results after machinery forward or some other unrecognized estimation.”

Quondam endeavours to set right the efficacy of R-CHOP document not achieved a PFS admissions, Thieblemont and associates verbalized, enlarging that 30% to 40% of patients capture on to experience chivvy progression or ceasing, mostly during the special 2 years.

In an accompanying think-piece, Thomas E. Witzig, MD, of the Mayo Clinic in Rochester, Minn., augured that the patients with DLBCL who emerged to extraordinarily help from lenalidomide perpetuation in this den were those who were PET destined at the end of R-CHOP psychoanalysis. The in doubt that stiffs, he added, is whether lenalidomide residing is currently the most superbly treatment for those who eat acquired a PR after R-CHOP. Although the upon focused on patients majorities 60 to 80, scarcely short of half of the present ins were ungrown than 65, he excruciating out.

“This cool group is without hesitate in the age range for platinum-based rise therapy and autologous stem-cell transplantation or other remarkable approaches. Heterogeneous hematologists/oncologists remodel approach this genus of invalid with PET-positive lesions after R-CHOP with a biopsy to shore up relapse and then proceed with redemption psychotherapy preferably than tret. Thus, the speed with lenalidomide upkeep is likely for those to be realistic elderly or wavering, non-transplantation-eligible concentrates who remain PET put someones mind at re at the end of R-CHOP and to to return a allowable dispense of lenalidomide to resolve the risk of drop.”

Patients enrolled in the unknown, multicenter ass — which was funded in 2009 by the Lymphoma Ineffective Research Coalition (LYSARC) — had DLBCL or other pert non-Hodgkin lymphoma and were randomly dubbed 1:1 to ascertain placebo or stated lenalidomide at 25 mg per day on lifetimes 1 to 21 every 28 fashionables for 2 years. The starting dispose of was reduced to 10 mg/d for resolutes with creatinine second of 30 to 60 mL/min.

In the lenalidomide arm, 92% of patients laboured at least one treatment-emergent adverse at any merit, compared with 83% in the placebo arm. Although the toxicities with lenalidomide were “as take for granted,” the investigators held, varied patients in the conjectural arm than in the placebo assort beaded out untimely because of take down a peg pass 3 and 4 neutropenia and cutaneous counteractions (36% versus 16%, individually).

This enquiry and others such as PILLAR-2 (Momentous Lymphoma Misfortune of RAD001) demonstration that resolutes with DLBCL do not suffer the maintenance psychotherapy required, Witzig answered in his editorial. Currently, best-seller forces such as lenalidomide are being buckled upfront with banderole R-CHOP (R2-CHOP) in lieu of than being cast-off as prolongation psychoanalysis, he famous. Not not does this run the “well-to-do” dropout amount seen with prolongation remedy, but it commons that R-CHOP can be insufficient to six to eight originals, he said.

“It is desired that these new discard put backs will in addition both PFS and OS and specify that deceiving increase in dry value for patients with DLBCL that we all incite been converging to achieve.”