Bendamustine And Adcetris In Untreated Hodgkin Lymphoma Of The Elderly
Topic: Hodgkin lymphoma — Clinical
Background:The treatment of Hodgkin Lymphoma (HL) in the elderly (eHL) remains challenging., due to a narrowtherapeutic window between effectiveness and toxicity of standard chemotherapy. Bendamustine (Be) andBrentuximab Vedotin (BV) are both well-tolerated and effective drugs in relapsing HL, but no data exist on BV-Be frontline treatment in the elderly.
Aims:The prospective, open-label, phase I/II HALO study was conducted (NationalTrial.Gov Id. 02467946) to testsafety and efficacy of BV-Be in untreated eHL.
Methods:Consecutively admitted, advanced-stage (IIB-IVB) patients (p.) aged 60 to 80 years, diagnosed with classical HLwere enrolled in five Italian and five French Institutions. The following Inclusion criteria had to be fulfilled: noprevious treatment, good performance status (ECOG ≤ 2), absolute neutrophil count (ANC)≥ 1.5 x 109/L (2)Hemoglobin ≥ 9 g/dL, (3) Platelets (PTL)≥ 100 x 109/L, (4) AST — ALT ≤ 2.5x ULN (5) Bilirubin ≤ 1.5 x ULN;(6) Creatinine < 150 μmol/l (or < 1.7 mg/dl), signed informed consent. P. underwent geriatric assessment withADL, IADL tests and CIRS co-morbidity scale upon interview by caregivers. Treatment consisted of 6 cycles ofthe BV-Be as follows: BV 1.2 mg/kg i.v. on day 1, and Bendamustine (Be) 90 mg/m2/day i.v. for two daysadministered every 3 weeks for a total of six courses. Filgrastim/Peg-filgrastim prophylaxis of neutropenia wasrecommended in all p. The primary study endpoint was safety during phase 1 and efficacy during phase 2.
Results:Since July 2015 till February 2019, 60 p. were consecutively enrolled in 5 French and 5 Italian centers, and onewas excluded from the analysis because of a histological revision consistent with angioimmunoblastic T-CellLymphoma. The mean age was 70.32 (62–79), and M/F ratio 41/18. The Ann-Arbor stage was IIB in 12, III in 14and IV in 33 p. and B-symptoms in 40. IPS was 0–2 in 19 and ≥ 3 in 40 patients, Performance Status (ECOG)was 0–1 in 53 and 2 in 6 patients. Despite an ADL score of 6 or more in 85% of p. and a IADL score of 8 in77.8% of p., the Cumulative Illness Rating Scale (CIRS) for co-morbidity, showed that (1) 38/54 (70%) had ≥ 5comorbidities, 15 of them (27%) with a score 3 (organ damage). Besides neutropenia and lymphopenia (134),severe (WHO 3–4) adverse events were infections (7), cutaneous reactions (5) and liver toxicity (2). No grade >2 peripheral neuropathy was observed. The infectious toxicity consisted in clinically documented CMV infectionin 5 cycles (3.1%) and febrile neutropenia in 3 cycles (1.8%)., Importantly, CMV reactivation was observed in 17(29%) p.: 12 received Valganciclovir and 4 (2 of them untreated) died with CMV viremia. Overall, 41/59 (69%)completed the treatment and 44/59 (75%) entered CR. A Complete Metabolic Response was achieved in 46/59(78%) p. The 2-y OS and PFS in intention-to-treat were 83% (95% CI 71–96) and 54% (95% CI 41–72) and inper-protocol 89% (95%CI 75–100) and 78% (95%CI 64–96), respectively. A PFS event was observed in 22: 5progressions (2 deaths), 17 relapses (8 deaths). Updated results with a longer p. follow-up will be presented.
Summary/Conclusion:BV-Be, when given in a full dose schedule and upon a strict monitoring of CMV reactivation is an effectiveregimen for unselected, untreated poor-risk elderly HL p. Out of 59 enrolled p., 46 (78%) achieved a completemetabolic response (CMR), 6 a partial metabolic response (PMR) and 3 had a Progressive Metabolic Disease