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Peer-reviewedCC BY 4.0Frontiers in Oncology

Progressive multifocal leukoencephalopathy, bispecific antibodies, and multiple myeloma: a case report and systematic review of the literature

  • Marina Tzanni1
  • Panagiotis Polyzoidis1
  • Konstantinos Angelopoulos1
  • Anastasia Skafida2
  • Ioanna Moustaka2
  • Athanasia Sepsa3
  • Pinelopi Korkolopoulou3
  • Georgios Velonakis4
  • Lampis C. Stavrinou5
  • Michail Voulgarelis1
  • Ioanna Stergiou1
  • Despina Fotiou1
5 affiliations
  1. 1Clinic & Laboratory of Pathophysiology, Department of Medicine, School of Health Sciences, National and Kapodistrian University of Athens
  2. 2Neurology Department, Laikon General Hospital
  3. 3First Department of Pathology, National and Kapodistrian University of Athens, Laikon General Hospital
  4. 4Research Unit of Radiology - 2nd Department of Radiology, National and Kapodistrian University of
  5. 5Second Dept. of Neurosurgery, National and Kapodistrian University of Athens
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Abstract

Background: Bispecific antibodies (BsAbs) have transformed outcomes in relapsed/refractory multiple myeloma (RRMM) but carry a substantial, sustained infectious burden, including rare cases of progressive multifocal leukoencephalopathy (PML).

Methods: We present an index case of a patient with RRMM treated with BsAbs diagnosed with PML complicated by immune reconstitution inflammatory syndrome (PML-IRIS) and perform a systematic review of the literature contextualizing this case among all published reports of PML and PML-IRIS following BsAb therapy in multiple myeloma (MM).

Case presentation: We report a 65-year-old woman with triple-class-refractory λ light-chain MM who was sequentially treated with the anti-B-cell membrane antigen (BCMA)×CD3 BsAb elranatamab and, subsequently, the anti-GPRC5D×CD3 BsAb talquetamab. During the second cycle of talquetamab, she developed rapidly progressive confusion, visual disturbance, and generalized tonic–clonic seizures. Cerebrospinal fluid JC virus (JCV) polymerase chain reaction (PCR) was negative on two occasions despite a clinical and radiographic course highly suggestive of PML; brain biopsy confirmed PML-IRIS. Despite talquetamab discontinuation, IVIG, mirtazapine, and compassionate-use nivolumab, the patient achieved only transient neurological stabilization and died 2 months after presentation.

Results: A systematic review of the literature identified 16 additional sources describing 29 patients with PML or PML-IRIS following BsAb therapy for MM, confirmed on full-text review to represent distinct individuals with no duplication between reports. BCMA-directed constructs accounted for most implicated agents, and talquetamab was implicated only in patients with prior or concurrent BCMA-directed exposure. PML-IRIS was documented in two of these patients and could not be excluded in a third. Despite uniformly supportive management, PML-attributable mortality was 89% (25/28) among patients with a definitive reported outcome, including the index case.

Conclusion: PML, and PML-IRIS specifically, is an emerging, likely class-level complication of BsAb therapy in MM. Clinicians should maintain a low threshold for neuroimaging and CSF JCV testing. These findings should be interpreted in light of the substantial clinical benefit that BsAbs provide in this heavily pretreated population.

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Cite

BibTeXRIS
BibTeX
@article{tzanni2026progressive,
  title = {{Progressive multifocal leukoencephalopathy, bispecific antibodies, and multiple myeloma: a case report and systematic review of the literature}},
  author = {Marina Tzanni and Panagiotis Polyzoidis and Konstantinos Angelopoulos and Anastasia Skafida and Ioanna Moustaka and Athanasia Sepsa and Pinelopi Korkolopoulou and Georgios Velonakis and Lampis C. Stavrinou and Michail Voulgarelis and Ioanna Stergiou and Despina Fotiou},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1935696},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1935696/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Progressive multifocal leukoencephalopathy, bispecific antibodies, and multiple myeloma: a case report and systematic review of the literature
AU  - Marina Tzanni
AU  - Panagiotis Polyzoidis
AU  - Konstantinos Angelopoulos
AU  - Anastasia Skafida
AU  - Ioanna Moustaka
AU  - Athanasia Sepsa
AU  - Pinelopi Korkolopoulou
AU  - Georgios Velonakis
AU  - Lampis C. Stavrinou
AU  - Michail Voulgarelis
AU  - Ioanna Stergiou
AU  - Despina Fotiou
PY  - 2026
DA  - 2026/10/28
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1935696
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1935696/full
AB  - Background: Bispecific antibodies (BsAbs) have transformed outcomes in relapsed/refractory multiple myeloma (RRMM) but carry a substantial, sustained infectious burden, including rare cases of progressive multifocal leukoencephalopathy (PML).  Methods: We present an index case of a patient with RRMM treated with BsAbs diagnosed with PML complicated by immune reconstitution inflammatory syndrome (PML-IRIS) and perform a systematic review of the literature contextualizing this case among all published reports of PML and PML-IRIS following BsAb therapy in multiple myeloma (MM).  Case presentation: We report a 65-year-old woman with triple-class-refractory λ light-chain MM who was sequentially treated with the anti-B-cell membrane antigen (BCMA)×CD3 BsAb elranatamab and, subsequently, the anti-GPRC5D×CD3 BsAb talquetamab. During the second cycle of talquetamab, she developed rapidly progressive confusion, visual disturbance, and generalized tonic–clonic seizures. Cerebrospinal fluid JC virus (JCV) polymerase chain reaction (PCR) was negative on two occasions despite a clinical and radiographic course highly suggestive of PML; brain biopsy confirmed PML-IRIS. Despite talquetamab discontinuation, IVIG, mirtazapine, and compassionate-use nivolumab, the patient achieved only transient neurological stabilization and died 2 months after presentation.  Results: A systematic review of the literature identified 16 additional sources describing 29 patients with PML or PML-IRIS following BsAb therapy for MM, confirmed on full-text review to represent distinct individuals with no duplication between reports. BCMA-directed constructs accounted for most implicated agents, and talquetamab was implicated only in patients with prior or concurrent BCMA-directed exposure. PML-IRIS was documented in two of these patients and could not be excluded in a third. Despite uniformly supportive management, PML-attributable mortality was 89% (25/28) among patients with a definitive reported outcome, including the index case.  Conclusion: PML, and PML-IRIS specifically, is an emerging, likely class-level complication of BsAb therapy in MM. Clinicians should maintain a low threshold for neuroimaging and CSF JCV testing. These findings should be interpreted in light of the substantial clinical benefit that BsAbs provide in this heavily pretreated population.
SN  - 2234-943X
ER  -