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

Relapsed/Refractort (R/R) patients with DLBCL have heterogeneous outcomes to subsequent treatment strategies. Refractory patients have poorer outcomes than relapsed patients. The retrospective SCHOLAR-1 multi-cohort study was carried out to assess outcomes of refractory DLBCL patients and to serve as a benchmark for clinical trials in this patient population in the future.

Refractory patients were defined as having PD or SD (duration of SD less than 1 year and at least 4 cycles of first-line or 2 cycles of later line therapy) as best response to chemotherapy, or patients who experienced relapse 1 year or less from ASCT.  Patients must have been treated with prior anti-CD20 monoclonal antibody and a prior anthracycline.

Data the LYSARC-CORAL and Canadian Cancer Trials Group-LY.12 phase III trials, as well as two observational cohorts (MD Anderson Cancer Center and Mayo Clinic/University of Iowa specialized Program of Research Excellence) were included in the SCHOLAR-1 analysis. Response rate (RR) and overall survival (OS) were estimated from start of salvage therapy.

Of a total of 861 DLBCL patients available for analysis, 597 patients had refractory disease.



(n =84)



Median agea (range)

55 (20, 79)

61 (20, 84)

54 (25, 68)

54 (19, 65)

RR (%)















RR by subgroup (%)

Primary refractory (n=142)





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





Relapse < 1 year post ASCT (n=149)





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 years old; Ly.12 study included subjects ≥16 years old; subjects >65 years were not recommended for inclusion. NA – due to study design.

In conclusion, the SCHOLAR-1 retrospective analysis found that patients with refractory DLBCL represent a significant unmet clinical need. These patients have homogenous outcomes, with a 20%-30% response rate and median OS of around 6 months. In the future, work needs to be undertaken to help us understand the biological and clinical factors which contributes to the plateau in outcomes of around a quarter of patients. Importantly, interpretation of clinical trial data in the relapse setting needs to take into account the additional time required for preparation of allogeneic bone marrow transplants and Chimeric Antigen Receptor (CAR) T-cell therapy, as well as in refractory patients the time for salvage therapy before experimental treatment commences. Lastly, it was stated that the assumption cannot always be made that heavily pretreated patients are poor prognosis patients.

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

Second Cancers (SCs) and late toxicities (including cardiovascular and neuro-psychiatric disorders) are common in surviving patients with NHL. There is a paucity in the knowledge concerning how novel agents such as rituximab impacts on late morbidity of patients, and so the SIMONAL study was conducted.

In 2015, fatigue (MFI-20) and Life Situation Questionnaires (LSQs) were sent to survivors treated in 12 randomized LYSA trials in DLBCL and FL which took place between 1993 and 2007. Of 8,113 patients who took part in the trials, 5,247 were alive at last follow-up. Of those who addresses were found for, 1,671 (50%) returned the questionnaires.

  • Responders were more likely from recent trials and were more often treated with rituximab than non-responders
  • NHL prognostic factors and chemotherapy were similar between responders and non-responders
  • Males = 906; females = 765 females
  • Median age = 64 years (range, 24–95)
  • FL = 28%; DLBCL = 72%
  • CHOP-like chemotherapy = 811 pts; high-dose = 518 pts; up-front ASCT = 342; rituximab combined to chemotherapy = 829 pts (50%)
  • Median follow-up = 11 years (range, 5–23)
  • No morbidity reported in 583 pts (35%)
  • The remaining, late events (1 to 7) were: cardiovascular disorders = 20%, neuro-psychiatric disorders = 17%, infections = 12%, musculoskeletal disorders = 11%, pulmonary diseases = 8%, digestive diseases = 5%, and SC = 8%
  • Rituximab was associated with less SC (6 vs. 9%; P = 0.02) and less cardiovascular disorders (17% vs. 23%; P = 0.006)
  • Up-front ASCT was associated with more infections (17% vs. 11%; P = 0.002) and more pulmonary diseases (12% vs, 7%; P = 0.005)
  • Age above 75 years (20%) was associated with more cardiovascular disorders and more SC
  • Persistant fatigue (MFI score ≥40) was experienced by 1,036 pts (64%)
  • There were no significant impact of any treatments
  • Increased fatigue level was associated (P < 0.001) with age, obesity, cardiovascular disorders, pulmonary diseases, musculoskeletal disorders, and neuro-psychiatric disorders 

The SIMONAL study is this first to document the altered health status of long-term NHL survivors. It was concluded that late morbidity and fatigue does not increase when patients are initially treated with chemotherapy combined with rituximab. Lastly, it was found that sociodemographic characteristics, BMI, increased fatigues, and comorbidities influenced the level of persistent fatigue.

  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).