A case of Multiple Myeloma in a Patient in Treatment for Chronic Lymphocytic Leukemia

Mario Biglietto1, Ugo Coppetelli2, Luciano Fiori2, Martina Gherardini1, Raffaele Maglione1, Alessandro Pulsoni1-2 and Azzurra Anna Romeo2.

1 Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
2 Hematology and Transplant Unit, Santa Maria Goretti Hospital, AUSL, Latina, Italy.

Correspondence to: Mario Biglietto. Via Benevento 6, Roma, Italy, 00161. E-mail: m.biglietto97@gmail.com  

Published: May 01, 2025
Received: February 18, 2025
Accepted: April 12, 2025
Mediterr J Hematol Infect Dis 2025, 17(1): e2025033 DOI 10.4084/MJHID.2025.033

This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

To the editor

We describe the case of a 58-year-old male patient diagnosed with Chronic Lymphocytic Leukemia (CLL) and Multiple Myeloma (MM), respectively, in 2016 and 2022. Characteristics of both diseases are summarized in Table 1. After 5 years of watching and waiting for CLL, in April 2021, investigations were conducted due to night sweats, lymphadenopathy, and progressive lymphocytosis (77620/mmc), revealing splenomegaly (LD = 18 cm) and enlarged supra- and sub-diaphragmatic lymph nodes on CT (ranging from 28x17 to 32x61 mm, with a 15 cm abdominal lymph node conglobate) and PET-CT scans (SUVmax 8.1). To exclude Richter's syndrome, a lymph node biopsy confirming CLL and a bone marrow biopsy were performed, confirming the diagnosis of CLL and revealing 10% of clonal plasma cells in the absence of SLIM-CRAB criteria, namely a Smouldering MM (SMM). Interphase FISH and NGS on peripheral blood lymphocytes showed unmutated-IGHV, absence of del17p, wt-TP53, and cr12 trisomy. Meeting treatment criteria for CLL, Acalabrutinib was started in November 2021, after initial debulking with Chlorambucil and prednisone for 7 days. This old therapy regimen was adopted as a bridge to Acalabrutinib while waiting for the drug to become available at the hospital pharmacy, in view of the high burden of the disease. In February 2022, after a hospitalization for SARS-CoV2-related pneumonia, Acalabrutinib was discontinued, and the patient lost to follow-up for 2 months. In May 2022, osteolytic lesions and spleen enlargement were reported. Interphase FISH analysis on clonal medullary plasma cells showed t(11;14) and 1q21 amplification. Meeting treatment criteria for MM, considering the patient transplant ineligible for comorbidities (Chronic Obstructive Pulmonary Disease, Pickwick syndrome, Congestive Heart Failure, Hypertension), treatment until progression with Venetoclax-Bortezomib-Dexamethasone (Ven-Vd) regimen, on the basis of the phase III BELLINI trial,[1] was started. Vd was administered as per the trial schedule, while Ven as prescribed for CLL, starting with 20 mg/day for 7 days, then increasing to 50 mg, 100 mg, 200 mg, and 400 mg per day for 7 days each, reaching a final dosage of 400 mg/day (Table 2). After 8 cycles, complete response (CR) for MM and Partial Response (PR) for CLL were reported (Figure 1). After 15 cycles, with sustained CR for MM, Bortezomib was withheld for grade 3 peripheral neuropathy. In December 2024, the patient died due to a rapid relapse of MM and concomitant pneumonia in the intensive care unit, retaining the CLL response.
Table 1 Table 1. Characteristics of CLL and MM.

Table 2 Table 2. Adjusted Ven-Vd.

FIgure 1 Figure 1.CLL response post-VIII Ven-Vd.
Synchronous and sequential diagnosis of MM and CLL/SLL is a rare event, with a few cases reported in the literature. Multiple studies were conducted in an attempt to prove a clonal relationship between the two diseases. However, different reports suggest that there may not be any clonal relationship between their cells of origin.[2-6] Nevertheless, we can hypothesize that some genes may have pleiotropic effects, and certain biological pathways may affect their mutual development due to the enrichment of B cell regulatory elements.[7-8]
The largest experience in the management of concomitant MM and CLL is reported by Ailawadhi S. et al.[8] From their experience, out of 10735 patients diagnosed with MM between 2000 and 2015, 28 (0.26%) also developed CLL: 15 before the diagnosis of MM, 11 simultaneously, and 2 after. None of them needed specific treatment for CLL, which resulted in responding to anti-myeloma treatment, and their prognosis was not statistically different from patients affected by MM only (58 vs 84 months, p = 0.198). Of note, in their experience, in 14 patients, MM and CLL were restricted to the same light chain. However, they did not attempt to identify a common origin cell or a clonal relationship. No prognostic differences were noted between patients with both diseases, regardless of whether they were restricted to the same light chain or not.
Our experience shows an optimal response for MM and CLL, both with a BELLINI trial-like therapy.[1] The reason for choosing this treatment regimen is the better results observed in relapsed/refractory MM (RRMM) carrying the t(11;14) (PFS 36.8 vs 23.4 months). The Venetoclax maximum dose was reduced (400 mg/day vs 800 mg/day), and a CLL-like ramp-up was performed in our case because of the high risk of hematological and infectious adverse events. In October 2023, we had to withhold Bortezomib for grade 3 peripheral neuropathy, and MM relapsed 14 months later, while CLL response had been retained.
We can conclude that, as already described, MM seems to be the main determinant of survival of this rare subgroup of patients. Ven-Vd could be a promising regimen in this setting. However, more data regarding safety and effectiveness are required. 

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