Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study

Abstract

In the CORAL study, 255 chemosensitive relapses with diffuse large B-cell lymphoma (DLBCL) were consolidated with autologous stem cell transplantation (ASCT), and 75 of them relapsed thereafter. The median time between ASCT and progression was 7.1 months. The median age was 56.1 years; tertiary International Prognosis Index (tIPI) observed at relapse was 0-2 in 71.6% of the patients and 42 in 28.4%. The overall response rate to third-line chemotherapy was 44%. The median overall survival (OS) was 10.0 months (median follow-up: 32.8 months). Thirteen patients received an allogeneic SCT, and three a second ASCT. The median OS was shorter among patients who relapsed o6 months (5.7 months) compared with those relapsing ⩾ 12 months after ASCT (12.6 months, P = 0.0221). The median OS in patients achieving CR, PR or no response after the third-line regimen was 37.7 (Po0.0001), 10.0 (P = 0.03) and 6.3 months, respectively. The median OS varied according to tIPI: 0-2: 12.6 months and 42: 5.3 months (P = 0.0007). In multivariate analysis, tIPI 42, achievement of response and remission lasting o6 months predicted the OS. This report identifies the prognostic factors for DLBCL relapsing after ASCT and thus helps to select patients for experimental therapy. INTRODUCTIONSalvage second-line chemotherapy followed by high-dose therapy and autologous stem cell transplantation (ASCT) is the standard of care for relapsed/refractory diffuse large B-cell lymphoma (DLBCL). In the CORAL study, two salvage regimens (R-DHAP (rituximab, dexamethasone, cytarabine, cisplatinum) or R-ICE (rituximab, ifosfamide, carboplatinum, etoposide)) were compared in 477 patients, and no difference was found. Only 50% of the patients could proceed to per protocol ASCT, afterwards they were randomly assigned to rituximab or observation. The 4-year event-free survival post ASCT was 52% and 53% for the rituximab and observation groups, respectively (P = 0.7). International Prognosis Index (IPI) at relapse, that is, secondary IPI (sIPI), independently predicted event-free survival, PFS and OS. Patients with DLBCL relapsing o 12 months after rituximab-containing first-line therapy were also identified as a subgroup with dismal outcome.

Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study

“…Smaller studies have shown that, similar to patients with DLBCL refractory to therapy in the more traditional sense, those who relapse early after receiving ASCT have poor outcomes. 13,23 This study was intended to globally characterize outcomes of patients for whom the most recent therapy was minimally effective. Our results confirm our assumptions built on these earlier studies, that patients do indeed have poor outcomes, regardless of refractory subgroup.…”

“…Results from clinical trials and retrospective cohort analyses identified by using a similar definition of refractory showed that these patients have consistently poor clinical outcomes. 13,[15][16][17][18][19][20][21][22][23] In 6 studies that assessed different chemotherapy regimens for 251 patients who had aggressive lymphoma refractory to first-line therapy, the objective response rate ranged from 0% to 23%, and the median OS was ,10 months. 15,[17][18][19][20]22 In an additional 3 studies of 135 patients whose lymphoma was refractory to second-line therapy, the objective response rate ranged from 1% to 14%, and the median OS was 5 months.…”

“…18,21,24 Finally, in 2 studies of patients who relapsed after ASCT, median OS of 8 months (n 5 45) and 10 months (n 5 75) were reported. 13,23 There is an urgent need for effective treatments for patients with refractory DLBCL whose disease fails to respond to immunochemotherapy or any subsequent salvage regimen and for those whose disease relapses early post-ASCT. A key component of any such effective treatment would be a high response rate, either durable unto itself or potentially offering the opportunity for consolidation with SCT.…”

Chimeric antigen receptor T-cell therapies for lymphoma

“…anti-CD20 monoclonal antibody rituximab and addition of this agent to conventional cytotoxic chemo therapy regimens has improved patient outcomes across multiple B-cell NHL subtypes [4][5][6] ; however, the prog noses of most patients with chemotherapy-refractory or multiply-relapsed B-cell NHL remain poor [7][8][9][10] . DLBCL is curable with first-line anthracycline-based immunochemotherapy regimens, typically R-CHOP (comprising rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), but a substantial number of patients have disease relapse, or primary-refractory lymphoma 8,11 ; the standard second-line approach is salvage chemotherapy followed by autologous haematopoietic stem-cell transplantation (auto-HSCT) 12,13 .…”

Update in Waldenström’s Macroglobulinemia

“…It is recommended in high risk WM with elevated lactate dehydrogenase indicating a high tumor burden. It should ideally be offered at early relapses [17]. Chemosensitivity at the time of transplant is the most important predictor of response [2].…”