High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years

Abstract

Autologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%; P ‫؍‬ .004). A PFS plateau was observed in the HDT group after 7 years. On multivariate analysis, OS and PFS were independently affected by the performance status score, the number of nodal areas involved, and the treatment group. Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs IntroductionFollicular lymphomas (FLs) are a subgroup of B-cell nonHodgkin lymphomas (NHLs) accounting for 15% to 30% of newly diagnosed lymphomas. [1][2][3] The natural history of this disease is characterized by a long survival that contrasts with systematic relapses. Many chemotherapy regimens have been used for treatment but have not improved long-term outcome, which depends on initial prognostic factors such as the Follicular Lymphoma International Prognostic Index (FLIPI), 4 response to first-line therapy, and minimal residual disease indicated by positivity of the bcl2 rearrangement on analysis of the polymerase chain reaction (PCR). Although new therapeutic approaches, including purine analogs and anti-CD20 monoclonal antibodies, have shown impressive response rates and prolonged progression-free survival (PFS), their effects on overall survival (OS) have yet to be confirmed. The major improvement in the management of FLs has been achieved by the use of the anti-CD20 monoclonal antibody rituximab, which improved OS in combination with chemotherapy in all 4 prospective, randomized studies published to date. [5][6][7][8][9] Before the era of monoclonal antibodies, autologous stem cell transplantation (ASCT) was evaluated as an alternative approach to standard chemotherapy. Numerous studies have shown encouraging results for patients with relapsed follicular NHL, [10][11][12][13] 10,15,16 The fourth study, from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO), compared chemotherapy to ASCT with rituximab in both arms. 17 In 2005 we published the results of the Groupe Ouest-Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS) 064 trial, showing a higher overall response rate and longer median event-free survival (EFS) in the high-dose therapy (HDT) group then the conventional chemotherapy group after a median follow-up of 5 years, with no difference in OS but a higher rate of secondary malignancies in the HDT group. 18 We report here the final results of this trial, after an extended follow-up period of 108 months (9 years...

Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma

“…On the one hand, it raises the possibility that a better control of the disease could postpone the use of therapy (such as mitoxantrone, fludarabine or autologous stem cell transplant conditioning regimen) at risk of secondary myeloid disorder in the relapse setting, but on the other hand, it could also be associated to the reduced course of cytotoxic therapy in the rituximab arm. 17,25,26 Nonetheless, it must be noted that no overall difference in the incidence of secondary malignancies was observed between the two arms of treatment. Even though progressive multifocal leukoencephalopathy is exceptional, its association with the use of rituximab is well documented.…”

Impact of the use of autologous stem cell transplantation at first relapse both in naive and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study

“…The recently published 10-year update of the GOELAMS 064 trial showed a plateau phase on the progression-free survival curve for transplanted patients which might suggest that HDC-ASCT could potentially cure some FL patients. 18 The reason for the absence of proven OS benefit is still unclear and may be related to the use of HDC-ASCT as salvage therapy for those patients who did not receive transplantation up front, or to long-term toxicities, including secondary malignancies occurring after HDC-ASCT. However, secondary malignancies have also been reported in non-transplanted patients.…”

The outcome of reduced intensity allogeneic stem cell transplantation and autologous stem cell transplantation when performed as a first transplant strategy in relapsed follicular lymphoma: an analysis from the Lymphoma Working Party of the EBMT

“…We have only included patients undergoing transplantation beyond first response, as this is the currently accepted indication for transplantation in FL. [18][19][20] A prospective study comparing auto-SCT with RIST in this setting unfortunately failed due to poor accrual, 16 and further prospective comparative studies in this setting are unlikely to be performed. Therefore, retrospective studies describing these two forms of transplant provide an important source of data.…”

“…[11][12][13][14][15] By contrast, auto-SCT is associated with a low early NRM of o5%. 2,3,[18][19][20] Late toxicities must also be taken into consideration when selecting a transplant strategy. Thus following an auto-SCT the development of secondary MDS (myelodysplastic syndrome)/AML has been reported in up to 10% of patients at 10 years post transplant.…”