ROB LOWN SOUTHAMPTON HODGKIN LYMPHOMA IN THE ELDERLY

ROB LOWN SOUTHAMPTON HODGKIN LYMPHOMA IN THE ELDERLY

EPIDEMIOLOGY HODGKIN LYMPHOMA - INCIDENCE

EPIDEMIOLOGY HODGKIN LYMPHOMA - MORTALITY

EPIDEMIOLOGY HODGKIN LYMPHOMA - MORTALITY BY AGE

NUMBER OF PEOPLE LIVING OVER 80 SET TO DOUBLE BY 2050, AND OVER 65 BY 50%. NHS England

TEXT BIOLOGY OF HL IN ELDERLY Nodular sclerosis dominates BUT less than in younger More mixed cellularity HL No convincing evidence latter does worse Typically higher ESR, B symptoms, lower PS, advanced stage and extra nodal sites (GSHG/Nebraska) Smaller volume disease

Credit David Plunkert, NYT

TEXT RATHL 1214 patients 43 over 65 years HD10 patients 138 aged 60-75 years

HOW APPLICABLE ARE CLINICAL TRIAL OUTCOMES IN THE ELDERLY TOO OFTEN, DOCTORS RESORT TO EXTRAPOLATION OR, TO PUT IT LESS POLITELY, GUESSING. New York Times

EARLY STAGE

TEXT EARLY STAGE DISEASE ABVD fit? If so then standard treatment approaches Unfit bleo risk anthracycline risk Comorbidity/frailty

DO WE NEED DACARBAZINE AND BLEO IN TREATMENT OF EARLY STAGE HL?

TEXT AVD? HD13 study 1:1:1:1* Non-inferiority de-escalation study, radiotherapy 30gy Concluded that omitting dacarbazine and bleo did not meet pre-set criteria for noninferiority Median age 38, 14% over 60 *recruitment to AV and ABV arms stopped early

HD13 FREEDOM FROM TREATMENT FAILURE

HD13 OVERALL SURVIVAL

TOXICITY ELDERLY SUBGROUP TOXICITY ANALYSIS Combined with HD10 Baseline PFTs done, pulmonary disease excluded Bleo toxicity RARE with 2 cycles of ABVD (1.5%) but 10% in those receiving 4 ABVD Can ABVD then be given safely in older patients with early disease and negative PET after two cycles? Combined modality treatment therefore extremely useful in this cohort Boll et all, Blood 2016

TEXT SHIELD Prospective non-randomised, over 60s, 175pts VEPEMB vs physician choice if patient too frail. RT for early stage Incorporated co-morbidity scale (ACE-27) 3yr PFS 74%, OS 81%. No frail patients achieved CR

ECOG HD6 RADIOTHERAPY ALONE Meyer et al, NEJM 2012

TEXT OTHER OPTIONS ChlVPP CHOP (some limited efficacy data) Radiotherapy alone

EARLY HL CHLVPP/EVA Derived from MOPP/ABVD Hybrid alternating regimen, 28 day cycle day 1 ChlVPP Day 8 EVA (etop/vinb/dox) 2 cycles then PET and RT 20Gy Data vs ABVD in advanced disease. Only compared to VAPEC-B in early stage. Guessing

TEXT SUMMARY - EARLY HODGKIN Standard approaches if fit Anthracyclines likely to be key to curative treatment Bleo sparing regiment if pulmonary toxicity risk high AVD not far behind ABVD Consider ChlVPP/EVA ChlVPP and/or RT in frail

ADVANCED HODGKINS

TEXT Again - fit for ABVD BEACOPP fit? NB 21% TRM in BEACOPP in HD9 vs 8% COPP/ABVD If yes, then standard treatment pathway?alternatives in unfit/frail patients.

TEXT SOUTHAMPTON APPROACH If older but fit, and no contraindication to anthracycline ChlVPP/EVA (Johnson et al, 2005 - equivalent to ABVD) de-escalation to AVD after 2 cycles as per RATHL Proven treatment that avoids bleomycin Anthracycline unfit ChlVPP alone

TEXT OTHER CONVENTIONAL OPTIONS VEPEMB - 3 yr PFS 58%, OS 66% (SHIELD) VEPEMB vs ABVD - More CR and better PFS/OS for ABVD, small study (Zallio et al) PVAG, BACOPP - more intensive, toxicity. 8% bleo tox with BACOPP. None are likely to be more tolerable than ABVD, and no good evidence they are more effective

TEXT NOVEL APPROACHES - BRENTUXIMAB BREVITY 60y over, ECOG 3 or less Stage III-IV disease 4xBV CMR - 26%, ORR 84% Median PFS 7.4m High rates of PN, gd III-IV tox

BV ECHELON-1 ABVD vs AAVD >60 subgroup AAVD equally effective, spares bleomycin toxicity Possibly more effective in stage IV disease, good option for BEACOPP unfit? COST, not yet funded in UK

TEXT OTHER BV-CHEMO COMBINATIONS Evens et al, 2017 2xBV followed by 6xAVD 2yr PFS 85%, OS 94% Yasenchak et al, 2015 BV plus benda or dacarbazine Benda combo toxic++ so stopped BV-dacarbazine CR rate 62%, other outcomes pending BCAP CHOP with BV substituting vincristine

TEXT CHECKPOINT BLOCKADE Efficacy for Pembro, nivo established No licence currently in first line Trials Nivo + AVD Pembro + AVD Nivo +BV

RELAPSE

TEXT CONVENTIONAL APPROACHES Very difficult to cure refractory or early relapsed disease in patients unfit for intensive salvage may be some hope with >1 yr relapse alternative combination regimens can be considered in individual cases

TEXT NOVEL AGENTS BV CDF funded after two prior systemic therapies (i.e. RT excluded including auto-ineligible up to 16 cycles

TEXT PEMBROLIZUMAB Recently approved by NICE via CDF following 2 systemic chemotherapy and BV 3-weekly up to 2 year or 35 doses, whichever takes longer Chen et al, JCO 2017

PREDICTING TOXICITY

TEXT ROLE OF ONCO-GERIATRICS Comprehensive geriatric assessments?fit for systemic therapy, stratification of treatment options optimisation of comorbidity management polypharmacy enhancement of social support adherence to therapy Could be incorporated into clinical trials

AND FINALLY FUTURE IMPLICATIONS Capacity and pressure on oncology services Older population, more complications, LOS etc Shrinking NHS budget, Falling standards of social care Tolerable therapies expensive