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R. Bruna et al.
Discussion
The present study reports outcomes after a median 13 years of follow up of a multicenter prospective trial compar- ing high-dose chemotherapy and autograft versus CHOP chemotherapy, both delivered with rituximab (R-HDS vs. CHOP-R), as upfront therapy in high-risk FL patients. To our knowledge, this follow up is the longest ever reported for first-line treatment of FL with rituximab-supplemented chemotherapy. The prolonged observation shows an extraordinary improvement in OS compared to the pre-rit- uximab era.15,16 The survival was similar in both treatment arms, confirming over the long-term our preliminary obser- vation that R-HDS does not add survival advantages com- pared to CHOP-R in the upfront therapy of high-risk FL.9 CR achievement was the most important factor for pro- longed survival. The importance of disease response is fur- ther emphasized by the first-time observation that MR achievement is associated with survival duration and a high proportion of patients had prolonged survival in the absence of disease recurrence.
The GITMO-IIL trial was designed for patients with high-risk FL, histologically diagnosed according to the Revised European-American Classification of Lymphoid Neoplasms (REAL)/World Health Organization (WHO) lymphoma classification.14 The FL diagnosis was confirmed by the high rate of BCL-2 gene translocation detected in patients with molecular assessment. The high-risk presen- tation was proved using the clinical prognostic scores avail- able when the protocol was designed.15-16 The subsequently developed FLIPI score employs other clinical parameters, and a proportion of our patients were not true “high risk” according to FLIPI.28 Nevertheless, all study patients clearly belonged to a severely ill population, with a 5-year survival expectancies of 43.6% (age-adjusted IPI score) and 38% (Italian Lymphoma Intergroup score), according to treat- ment available at the time the trial was conceived.15,16 The 13-year survival of 66.4% recorded in our series represents a marked improvement in life expectancy compared to sur- vival reported in the pre-rituximab era for similar high-risk FL patients. This result is especially notable because only
Figure 5. Updated event-free survival (EFS) and progression-free survival (PFS) according to treatment arms. Intensive chemoimmunotherapy with autograft (R-HDS) versus conventional chemoimmunotherapy (CHOP-R). (A) EFS. (B) PFS. No: number; yrs: years.
four rituximab doses were applied to the majority of patients, and the treatment schedule was not that most fre- quently delivered in present times.
Recently, two other prospective trials performed in advanced-stage FL with rituximab-based upfront regimens have been updated: the Italian FOLL05 study comparing R- CVP, R-CHOP, and R-FM and the SWOG study comparing R-CHOP versus CHOP followed by radioimmunothera- py.29,30 Both the FOLL05 study, with 8-year OS of 83%, and the SWOG study, with 10-year OS of 78%, showed extended life expectancies in the absence of rituximab maintenance. These values are in line with our 13-year OS of 66% obtained in a selected group of high-risk FL. The results strengthen the observations from several retrospec- tive studies showing prolonged survival in FL following immunochemotherapy.10-13 Moreover, results from all of these studies indicate that the CHOP schedule delivered
Figure 4. Updated disease-free survival (DFS) according to treatment arms.
Intensive chemo-immunotherapy with autograft (R-HDS) vs. conventional chemoimmunotherapy (CHOP-R). No: number; yrs: years.
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haematologica | 2019; 104(11)