PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY DURING TECLISTAMAB THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA
- 1Hospital Moinhos de Vento, Porto Alegre, RS, Brasil
Abstract
Background: Teclistamab, a BCMAxCD3 bispecific antibody, has improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, prolonged exposure might result in sustained immune dysfunction, increasing susceptibility to opportunistic infections. Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV) reactivation, is a rare but often fatal demyelinating infection of the central nervous system. Data regarding immune checkpoint inhibition as a therapeutic strategy for therapy-associated PML remain limited. Aim: To describe PML developing during teclistamab therapy for RRMM and to evaluate the clinical and radiological response following PD-1 blockade (pembrolizumab). Methods: Clinical course, diagnostic findings, and management were retrospectively analyzed. Results: A 72-years-old man with IgA kappa multiple myeloma diagnosed in 2018. His first-line treatment was bortezomib, cyclophosphamide and dexamethasone (VCD), followed by autologous hematopoietic stem cell transplantation (AHSCT) and maintenance therapy with lenalidomide. In 2019, with biochemical relapse, he was treated with daratumumab, lenalidomide, and dexamethasone (DRd) until September 2023, when he had disease progression while on therapy and started teclistamab combined with monthly intravenous immunoglobulin replacement. He achieved complete response with minimal residual disease negativity in 2024, undetectable free light chains and no monoclonal spike. During BCMA therapy, he developed recurrent sinusitis and intestinal cytomegalovirus infection. In mid-2025, he presented with psychomotor agitation, mixed aphasia and apraxia. Brain MRI revealed left temporal and frontal lesions measuring approximately 5.3 × 3.1 cm in the largest axial dimensions and 3.7 cm in the craniocaudal axis, with T2/FLAIR hyperintensity and peripheral diffusion restriction (Figure 1). Magnetic resonance spectroscopy supported an inflammatory-demyelinating process. Cerebrospinal fluid PCR was positive for JC virus, establishing the diagnosis of PML. At that time, there was no evidence of myeloma progression. Teclistamab was discontinued and pembrolizumab was initiated in October 2025 (every 21 days). Following PD-1 blockade, the patient demonstrated progressive neurological improvement, and repeat MRI in January 2026 showed partial lesion regression (Figure 2). Subsequent reassessment revealed a new osteolytic lesion at C4 and alternative antimyeloma therapy with talquetamab has been started. Conclusion: This case illustrates the potential role of PD-1 blockade in restoring antiviral immune surveillance in PML associated with BCMA-directed therapy. The temporal association between pembrolizumab initiation and both clinical and radiological improvement supports immune reconstitution as a plausible therapeutic mechanism. Antiviral immune recovery may occur at the expense of myeloma control, underscoring the complex balance between infection management and oncologic efficacy. Prospective evaluation of checkpoint inhibition in therapy-associated PML is warranted.
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BibTeX
@article{navroski2026progressive,
title = {{PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY DURING TECLISTAMAB THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA}},
author = {Sabrina NAVROSKI and Pedro D'elia Machado SILVA and Erica Marquardt Lammerhirt OTTONI and Gustavo Costa FERNANDES},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107921},
url = {https://doi.org/10.1016/j.htct.2026.107921},
note = {CC BY},
}
RIS
TY - JOUR
TI - PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY DURING TECLISTAMAB THERAPY IN RELAPSED/REFRACTORY MULTIPLE MYELOMA
AU - Sabrina NAVROSKI
AU - Pedro D'elia Machado SILVA
AU - Erica Marquardt Lammerhirt OTTONI
AU - Gustavo Costa FERNANDES
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107921
UR - https://doi.org/10.1016/j.htct.2026.107921
AB - Background: Teclistamab, a BCMAxCD3 bispecific antibody, has improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, prolonged exposure might result in sustained immune dysfunction, increasing susceptibility to opportunistic infections. Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV) reactivation, is a rare but often fatal demyelinating infection of the central nervous system. Data regarding immune checkpoint inhibition as a therapeutic strategy for therapy-associated PML remain limited. Aim: To describe PML developing during teclistamab therapy for RRMM and to evaluate the clinical and radiological response following PD-1 blockade (pembrolizumab). Methods: Clinical course, diagnostic findings, and management were retrospectively analyzed. Results: A 72-years-old man with IgA kappa multiple myeloma diagnosed in 2018. His first-line treatment was bortezomib, cyclophosphamide and dexamethasone (VCD), followed by autologous hematopoietic stem cell transplantation (AHSCT) and maintenance therapy with lenalidomide. In 2019, with biochemical relapse, he was treated with daratumumab, lenalidomide, and dexamethasone (DRd) until September 2023, when he had disease progression while on therapy and started teclistamab combined with monthly intravenous immunoglobulin replacement. He achieved complete response with minimal residual disease negativity in 2024, undetectable free light chains and no monoclonal spike. During BCMA therapy, he developed recurrent sinusitis and intestinal cytomegalovirus infection. In mid-2025, he presented with psychomotor agitation, mixed aphasia and apraxia. Brain MRI revealed left temporal and frontal lesions measuring approximately 5.3 × 3.1 cm in the largest axial dimensions and 3.7 cm in the craniocaudal axis, with T2/FLAIR hyperintensity and peripheral diffusion restriction (Figure 1). Magnetic resonance spectroscopy supported an inflammatory-demyelinating process. Cerebrospinal fluid PCR was positive for JC virus, establishing the diagnosis of PML. At that time, there was no evidence of myeloma progression. Teclistamab was discontinued and pembrolizumab was initiated in October 2025 (every 21 days). Following PD-1 blockade, the patient demonstrated progressive neurological improvement, and repeat MRI in January 2026 showed partial lesion regression (Figure 2). Subsequent reassessment revealed a new osteolytic lesion at C4 and alternative antimyeloma therapy with talquetamab has been started. Conclusion: This case illustrates the potential role of PD-1 blockade in restoring antiviral immune surveillance in PML associated with BCMA-directed therapy. The temporal association between pembrolizumab initiation and both clinical and radiological improvement supports immune reconstitution as a plausible therapeutic mechanism. Antiviral immune recovery may occur at the expense of myeloma control, underscoring the complex balance between infection management and oncologic efficacy. Prospective evaluation of checkpoint inhibition in therapy-associated PML is warranted.
SN - 2531-1379
SN - 2531-1387
ER -