FL |DLBCL

ASCO 2016 Poster Discussion - Long Term Toxicity and Fatigue After Treatment for non-Hodgkin Lymphoma (NHL): An Analysis of Twelve Collaborative Lymphoma Study Association (LYSA) Trials, The Simonal Study

The ‘Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia’ poster discussion session took place on Monday June 6, 2016, between 13:15–14:45. The session was jointly chaired by Susan Mary O’Brien, MD, Associate Director for Clinical Science, at Chao Comprehensive Cancer Center in the University of Irvine, California, and John Leonard, MD, ofWeill Cornell Medicine, New-York.

Dr Grzegorz Nowakowski, MD of the Mayo Clinic Lymphoma Group discussed the abstracts 7516 and 7518 during the poster discussion “Outcomes from Large Databases”.

Abstract 7516: Outcomes in Refractory Aggressive Diffuse Large B-Cell Lymphoma (DLBCL): Results from the International SCHOLAR-1 Study

Background: Patients with relapsed/refractory DLBCL have heterogeneous outcomes to subsequent therapy. The subgroup of these patients with refractory disease (r-DLBCL) have a worse prognosis. A multi-cohort study, SCHOLAR-1 (Retrospective Non-Hodgkin Lymphoma Research) was performed to evaluate outcomes for patients with r-DLBCL and serve as a benchmark for future clinical trials in this population.

 

Methods: Eligible subjects had r-DLBCL defined as progressive disease (PD) or stable disease (SD) as best response to chemotherapy (duration of SD <12 mos and at least 4 cycles of first-line or 2 cycles of later line therapy) or relapse ≤12 mos of ASCT. Patients must have received an anti-CD20 monoclonal antibody (unless CD20-) and an anthracycline as one of their prior regimens. Data from 2 phase 3 studies (LYSARC-CORAL and Canadian Cancer Trials Group-LY.12), and 2 observational cohorts (MD Anderson Cancer Center (MDACC), and Mayo Clinic / University of Iowa (MC/IA) Specialized Program of Research Excellence) were integrated. Response rate (RR) and overall survival (OS) were estimated from start of salvage therapy.

Results: Data for 861 patients with DLBCL were available for analysis and 597 patients with r-DLBCL were identified, with subgroups and outcomes shown in the table. An integrated analysis of outcomes will be presented.

Conclusions: In this large multi-center dataset, patients with r-DLBCL have homogenous outcomes with a response rate of 20%-30% and median overall survival of approximately 6 mos. This consistently poor outcome represents a significant unmet medical need.

 

MDACC
(n=152)

MC / IA
(n =84)

CCTG LY.12
(n=190)

CORAL
(n=171)

Median agea (range)

55 (20, 79)

61 (20, 84)

54 (25, 68)

54 (19, 65)

RR (%)

19

23

24

36

CR

7

8

2

18

PR

13

14

23

18

RR by subgroup (%)

       

Primary refractory (n=142)

NA

28

24

NA

Refractory to > 2nd line therapy (n=306)

19

26

NA

36

Relapse < 1 year post ASCT (n=149)

21

11

NA

35

Median OS (Q1, Q3) - mos

6.9 (5.8, 8.2)

4.6 (3.9, 5.8)

6.8 (5.8, 8.2)

6.7 (5.6, 8.8)

 

aCORAL included subjects 18 – 65, Ly.12 studies included subjects ≥ 16; subjects > 65 were not recommended for inclusion. NA – due to study design.

Abstract 7518Long Term Toxicity and Fatigue After Treatment for non-Hodgkin Lymphoma (NHL): An Analysis of Twelve Collaborative Lymphoma Study Association (LYSA) Trials, The Simonal Study

Background: NHL survivors are at high risk for second cancers (SC) and late toxicities such as cardiovascular (CV) or neuro-psychiatric (NP) disorders. Little is known about new agents such as rituximab (RITUX). The impact of treatment regimens on late morbidity was analyzed in a large cohort of survivors with long follow-up (FU).

Methods: In 2015, a fatigue (MFI-20) and a self-assessment Life Situation Questionnaire (LSQ) were mailed to survivors treated in 12 successive LYSA randomized trials (1993-2007) for Diffuse Large B cell (DLBCL) and follicular (FL) lymphomas. Of 8113 pts enrolled into trials, 5247 were alive at last FU. Addresses were obtained for 3317 survivors of whom 1671 (50%) returned the questionnaires. Responders more often came from recent trials and were more often treated with RITUX than non-responders. NHL prognostic factors and chemotherapy were similar in both groups. Linear regression models were used to assess factors linked to increased fatigue level.

Results: There were 906 males and 765 females (median age 64 yrs; 24 to 95). 28% had FL and 72% DLBCL. 811 pts received CHOP-like chemotherapy, 518 high-dose CHOP and 342 up-front autograft consolidation (ASCT). RITUX was combined to chemotherapy in 829 pts (50%). Median FU was 11 yrs (5 to 23). 583 pts (35%) reported no morbidity. For the remaining, late events (1 to 7) were: CV in 20%, NP in 17%, infections in 12%, musculoskeletal (MSk) disorders in 11%, pulmonary (Pulm) diseases in 8%, digestive diseases in 5% and SC in 8%. RITUX was associated with less SC (6 vs 9%, p = 0.02) and less CV (17 vs 23%, p = 0.006). Up-front ASCT was associated with more infections (17 vs 11%, p = 0.002) and more Pulm (12 vs 7%, p = 0.005). Age above 75 (20%) was only associated with more CV and more SC. 1036 pts (64%) expressed persistent fatigue (MFI score ≥ 40). There were no significant impact of any treatments. Increased fatigue level was associated (p < 0.001) with age, obesity, CV, Pulm, MSk and NP.

Conclusions: This first study reporting on long-term NHL survivors confirmed an altered health status. Initial combination of chemotherapy and RITUX does not increase late morbidity and fatigue. Clinical trial information: pooled trials already registered.

References
  1. Crump M, et al. Outcomes in refractory aggressive Diffuse Large B-Cell Lymphoma (DLBCL): results from the international SCHOLAR-1 study. J Clin Oncol 34, 2016 (suppl; abstr 7516).
  2. Mounier N, et al. Long term toxicity and fatigue after treatment for non-Hodgkin Lymphoma (NHL): an analysis of twelve collaborative lymphoma study association (LYSA) trials, the Simonal study. J Clin Oncol 34, 2016 (suppl; abstr 7518).