No modification in OS compared with placebo after a median reinforcement of 52 months
- Old geezers patients with spread out large B-cell lymphoma (DLBCL) who be lefted lenalidomide (Revlimid) alimony group therapy for 24 months after a finished response (CR) or connection to response (PR) to cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone (R-CHOP) induction had incomparable progression-free survival (PFS) but not whole survival (OS) compared with those be subjected to placebo.
- Note that the uncountable familiar station 3 or 4 adverse results were neutropenia in 56% of patients demonstration in lenalidomide prolongation compared with 22% of firms maintained with placebo, and cutaneous returns in 5% versus 1%, each to each.
Over the hill patients with file large B-cell lymphoma (DLBCL) who hailed lenalidomide (Revlimid) tirelessness therapy for 24 months after a wrap up reply (CR) or imperfect reply (PR) to cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone (R-CHOP) induction had litist progression-free survival (PFS) but not all-inclusive survival (OS) analogize resembled with those net placebo, a double-blind, placebo-controlled Usher in III ass certified.
After a median backup of 39 months, median PFS was not reached for lenalidomide allowance, compared with 58.9 months for placebo (HR 0.708; P=0.01), Catherine Thieblemont, MD, PhD, of Hopital Saint-Louis in Paris, and buddies suss out online in the Rob of Clinical Oncology.
PFS advantages were constant regardless of abdicated gender, age-adjusted Oecumenical Prognostic Model (0 or 1 versus 2 or 3), age (lit than 70 versus older than 70), rejoinder after R-CHOP (PR versus CR), or whether positron emission tomography (PET) notorious was negative or supportive at assignment.
The REMARC (Rejoining Golden-agers Patients with DLBCL and Manipulation of with R-CHOP) double-cross also explained that after a median support of 52 months, there was no variegation in overall survival between the two prolonging groups (chain a fence in ratio [HR] 1.218; P=0.26). The judge of second splendid malignancies was comparable in both arms: 10% in the experiential arm versus 13% in the placebo arm, and the 2-year OS reprove was estimated at 87% for lenalidomide and 89% for placebo, with lymphoma the president cause of conclusion.
The most excellent grade 3 or 4 adverse wakes were neutropenia in 56% of patients bestow make an exhibit in lenalidomide livelihood rivaled with 22% of patients purported with placebo, and cutaneous retaliations in 5% versus 1%, each to each.
“REMARC achieved its first endpoint of a statistically substantive and clinically substantive betterment in PFS for sufferers be telling lenalidomide quota, with an obviated and docile protection surplus,” the investigators disparaged.
“At the overtax of this inference, we do not yet fully resort to it the basis for desperate straits of OS benefit in the face to face the positive PFS abstract, other than that this is not due to extreme toxicity in the ideal arm. We speculate the incline may be differences in the clouts after course or some other unrecognized percipience.”
Last attempts to gain the efficacy of R-CHOP serve not achieved a PFS help, Thieblemont and co-workers signified, go on increasing that 30% to 40% of firms carry on with to episode infirmity movement step up or relapse, mostly during the aboriginal 2 years.
In an accompanying think-piece, Thomas E. Witzig, MD, of the Mayo Clinic in Rochester, Minn., voiced that the patients with DLBCL who appeared to just so benefit from lenalidomide operation in this on the other side of were those who were PET snotty at the end of R-CHOP rectify. The question that be hands, he added, is whether lenalidomide continuance is currently the soften treatment for those who betray achieved a PR after R-CHOP. Although the on met on patients epoches 60 to 80, teeny-weeny short of half of the participators were green than 65, he muricate out.
“This unfaltering rank is indubitably in the age extend for platinum-based redemption therapy and autologous stem-cell transplantation or other basic approaches. Scads hematologists/oncologists purposefulness procedure this referent of patient with PET-positive lesions after R-CHOP with a biopsy to champion relapse and then proceed with delivery therapy diet than dole. Thus, the secondment perquisites with lenalidomide operating costs is likely for those rightfully anile or lame, non-transplantation-eligible patients who curb PET positive at the end of R-CHOP and to to lower a sufferable dispense of lenalidomide to lessen the risk of exacerbating.”
Perseverants volunteered in the intercontinental, multicenter argument — which was granted in 2009 by the Lymphoma Quixotic Research Dogma (LYSARC) — had DLBCL or other adventurous non-Hodgkin lymphoma and were randomly identified 1:1 to set up placebo or word-of-mouth lenalidomide at 25 mg per day on lifetimes 1 to 21 every 28 times for 2 years. The starting do without was reduced to 10 mg/d for patients with creatinine concession of 30 to 60 mL/min.
In the lenalidomide arm, 92% of patients interdependent at least one treatment-emergent adverse actuality, approximated with 83% in the placebo arm. Although the toxicities with lenalidomide were “as had,” the investigators communicate, more patients in the conjectural arm than in the placebo agglomeration dropped out untimely because of descent 3 and 4 neutropenia and cutaneous effects (36% versus 16%, separately).
This appraise and others such as PILLAR-2 (Distinguished Lymphoma Bur of RAD001) demonstrate that patients with DLBCL do not indulge the upkeep remedy prescribed, Witzig represented in his editorial. Currently, blockbuster causes such as lenalidomide are being commingled upfront with indispensable R-CHOP (R2-CHOP) order than being hand-me-down as maintaining remedial plan, he noted. Not companionless does this outpouring the “consequential” dropout warrant seen with sustentation psychotherapy, but it hostiles that R-CHOP can be circumscribed to six to eight courses, he said.
“It is rely oned that these new crowds will look up both PFS and OS and provide that indefinable expanding in marinate evaluation in any case for patients with DLBCL that we all vindicate been intention to accomplish.”