Safety and Efficacy of ThaDD Regimen in Very Elderly Patients with Multiple Myeloma (MM)
Authors: Offidani Massimo , Corvatta Laura , Piersantelli Maria-Novella , Polloni Claudia , Gentili Silvia , Galieni Piero , Visani Giuseppe , Alesiani Francesco , Catarini Massimo , Brunori Marino , Samori Arduino , Burattini Maurizio , Centurioni Riccardo , Ferranti Mario , Giuliodori Luciano , Candela Marco , Marconi Monica , Mele Anna , Leoni Pietro 
Published: April 2020

Multiple myeloma represents a typical disease of old age as reported by recent epidemiological data showing that the incidence of MM in persons aged above 75 years is more than 30%. Very elderly MM patients remain very difficult to treat since they more likely have comorbid medical conditions and a poor performance status, limiting the chance of chemotherapy administration. Moreover, this populations is often underrepresented in clinical trials and few studies are specifically designed for patients of old age. Besides these problems, it has to be underlined that not even the introduction of new agents (thalidomide, lenalidomide, bortezomib) has been able to improve survival in patients older than 70 years if compared with younger ones. The aim to this retrospecive study was to assess the safety and efficacy of ThaDD regimen (thalidomide 100 mg/day continously, pegylated liposomal doxorubicin 40 mg/m2 on day 1 for 6 28-day cycles, dexamethasone 40 mg on days 1–4 and 9–12) in 27 newly diagnosed MM patients older than 75 years.

In this group of patients median age was 77 years (range 75–91), performance status was poor in one third, 78% had ISS score ≥ 2, 37.5% showed unfavourable cytogenetics abnormalities and 30% impaired renal function. At least a PR and a VGPR were achieved in 85.5% and 52% of patients, respectively, with 15% of them obtaining a CR. After a median follow-up of 25 months (range 7–58), median PFS was 25 months. Two-year PFS and OS resulted 50% and 75%, respectively. More frequent grade 3–4 non hematological side effects were peripheral neuropathy (15%) and constipation (11%). A severe neutropenia was observed only in 4% of patients and in 2 patients (7.5%) occurred a febrile episode requiring antibiotic therapy. On thromboprophylaxis with fixed-dose warfarin, 5 patients (18.5%) developed a deep venous thrombosis and one patients with carotid arteriopathy experienced acute stroke. Two patients died early during treatment, because of acute liver failure and heart attack, respectively. No significant differences in term of toxicity were found between this group of patients and patients younger than 75 years receiving the same regimen although in these latter vascular events were twice as much and early mortality rate higher. Overall, the compliance with therapy was satisfactory and only one patient stopped treatment due to the occurrence of atrial fibrillation and deep venous thrombosis. Pegylated liposomal doxorubicin administration was delayed in one patient who developed fever and mucositis whereas in another patient dexamethasone dose was reduced because of miopathy. Thalidomide discontinuation was necessary in 2 patients due to severe neuropathy and pulmonary embolism, respectively.

Our study demonstrate that also MM patients older than 75 are able to derive benefit and to tolerate treatments used for younger patients although in very elderly vascular events seem to be more frequent and requiring maximal care. In patients with poorer performance status drugs adjusted-dose is probably needed to reduce early mortality.