Risk factors predicting outcomes for primary refractory hodgkin lymphoma patients treated with salvage chemotherapy and autologous stem cell transplantation

Abstract

Summary We aimed to identify risk factors that predict functional imaging (FI) response to salvage chemotherapy and evaluate outcomes following autologous stem cell transplant (ASCT) in primary refractory Hodgkin Lymphoma (HL). From 1 October 1994 to 10 July 2015, 192 primary refractory HL patients were treated on sequential second line protocols. Event-free survival (EFS) and overall survival (OS) were calculated from the date of histological confirmation of refractory disease. Covariates were analysed for relationship with FI response and EFS. By intent-to-treat, the median EFS was 8·9 years and OS 10·4 years with 41% having positive post-salvage FI. On multivariate analysis, the presence of B symptoms and bulk ≥5 cm predicted for positive FI, with odds ratios of 2·15 and 2·03, respectively. For the 167 (87%) transplanted patients, 60% had a negative pre-ASCT FI. Median EFS and OS were not reached with at a median follow-up of 3·6 years in surviving patients. Both stage IV refractory disease and persistent FI abnormality pre-ASCT were associated with worse outcomes: 3-year EFS was 84%, 54% and 28% for zero, 1 and 2 risk factors, respectively (P < 0·001). Further studies are needed to validate our prognostic model and to determine optimal therapy for patients with multiple risk factors.

A multi‐institutional analysis of peritransplantation radiotherapy in patients with relapsed/refractory Hodgkin lymphoma undergoing autologous stem cell transplantation

“…16,17 Disease was categorized as primary refractory if progression was noted during or within 3 months of upfront chemotherapy and was defined as relapsed if disease progression occurred >3 months after the completion of initial therapy.…”

Sequential immunotherapy in a patient with primary refractory Hodgkin lymphoma and novel mutations

“…High dose chemotherapy with autologous stem cell transplant is considered standard of care for relapsed patients with improved PFS but questionable OS benefit over conventional rescue chemotherapy regimens [ 5 , 19 , 20 ]. Shortened time between first diagnosis and relapse (<12 months), anemia, B symptoms, bulk at initial presentation, involvement of extranodal sites [ 5 ] as well as positive 18 FDG PET [ 21 ], >3 salvage regimens and chemoresistance predict high risk and unfavorable course. Even with autotransplant, only 41% of patients with a high risk score were progression free after 4 years in a recent study [ 22 ].…”

“…Even with autotransplant, only 41% of patients with a high risk score were progression free after 4 years in a recent study [ 22 ]. In groups of purely primary refractory patients, prognosis was even worse with 5 year OS rates of 36% [ 23 ] to 48% [ 24 ] and in case of simultaneously present poor risk factors 28% [ 21 ]. Due to the extremely poor prognosis of patients put on conventional chemotherapy (e.g.…”

“…This contrasts with the high efficacy of anti-PD1 and anti-CTLA4 strategies and may point to effector mechanisms of targeting PD1 and CTLA4 apart from restitution of CD8+ effector cells from exhaustion, like e.g. elimination of Treg cells [ 44 ] and evolution and diversification of the TCR repertoire [ 21 ] by anti-CTLA4 abs and inhibition of generation, maintenance and function of T reg cells [ 45 ] and expansion of NK cells by anti-PD1 targeting [ 46 ].…”

Advances in the pathophysiology and treatment of relapsed/refractory Hodgkin&rsquo;s lymphoma with an emphasis on targeted therapies and transplantation strategies

“… 8 , 139 , 140 , 142 – 144 Although primary refractory HL is thought to confer worse prognosis, such patients may also derive benefit from ASCT, depending on the risk factors present. 145 , 146 …”