Introduction
Multiple myeloma (MM) patients who are triple-class exposed and/or refractory to immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies are known to have extremely poor outcomes, with a median progression-free survival of approximately 4.6 months and a median overall survival of only 9–14 months [ 1 – 3 ]. In recent years, chimeric antigen receptor T-cell therapy and bispecific antibodies (BsAbs) have emerged as promising therapeutic options for patients with triple-class–exposed relapsed/refractory multiple myeloma (RRMM). In the MajesTEC-1 study, teclistamab has demonstrated remarkable efficacy even in heavily pretreated populations, with overall response rates (ORR) of 52.5% and 30.0% of patients achieving complete response (CR) or better [ 4 ]. Consistent depth of response and manageable safety profiles have also been confirmed in Japanese clinical settings [ 5 ].
A large multicenter retrospective study led by the International Myeloma Working Group Immunotherapy Committee evaluated 210 patients treated across nine academic centers in five countries. Notably, 71% of these patients would have been considered ineligible for the MajesTEC-1 trial due to prior BCMA-targeted therapy, severe renal dysfunction, profound cytopenias, or poor performance status. Despite this highly challenging clinical background, the ORR among evaluable patients was 67%, including 55% with very good partial response or better and 21% with CR or better, which is comparable to the results observed in the pivotal clinical trial [ 6 ].
However, subgroup analyses from the MajesTEC-1 trial revealed that patients with true extramedullary disease (EMD) represent a particularly difficult-to-manage population, demonstrating an ORR of only 35.7% and ≥ CR in 17.9%, which compares unfavorably with other high-risk subgroups [ 7 ]. Against this background, we report what to our knowledge is the first reported case of pulmonary parenchymal extramedullary involvement in RRMM successfully treated with teclistamab.
Case
A 74-year-old man with a medical history of diabetes mellitus and dyslipidemia presented in March 2023 with multiple osteolytic lesions involving the sphenoid sinus, C2 and T8 vertebrae, the ninth rib, left scapula, right sacrum, right pubis, and right femur. He was diagnosed with IgA-κ multiple myeloma. Bone marrow examination revealed ≥ 70% clonal plasma cells. Cytogenetic studies were negative for del(17p), t(4;14), t(14;16), and gain of 1q21. The disease was classified as ISS stage II and R-ISS stage II.
Combination therapy with an anti-CD38 antibody, immunomodulatory drug, and dexamethasone was initiated in April 2023. However, disease progression was noted due to the development of a new sacral lesion. Following local radiotherapy to this lesion, ixazomib, lenalidomide, and dexamethasone were commenced, but serum IgA continued to rise, indicating further progression. In January 2025, isatuximab, carfilzomib, and dexamethasone were administered for three cycles. However, approximately six weeks after achieving a partial response, the left posterior pharyngeal soft-tissue lesion and multiple pulmonary nodules showed rapid progression, with new bilateral hilar lymphadenopathy and a subcutaneous mass in the left upper abdomen. Serum IgA increased by approximately 500 mg/dL during this period. In the absence of microbiological evidence of infection, including negative sputum cultures and β-D-glucan, these findings were considered consistent with disease progression. Bronchoscopic biopsy was not pursued due to the risk of treatment delay and potential deterioration of respiratory status.
At that time, laboratory values were as follows: WBC 4,170/µL, hemoglobin 10.8 g/dL, platelet count 181 × 10⁹/L, LDH 403 U/L, IgG 256 mg/dL, IgA 980 mg/dL, and serum free light chains κ/λ 23.5/0.5 mg/L. The patient received 35 g of intravenous immunoglobulin and one cycle of CHOP chemotherapy. In April 2025, at the age of 76 years with an Eastern Cooperative Oncology Group performance status of 2, treatment with teclistamab was initiated as fifth-line therapy. No notable adverse events occurred following the first step-up dose of 0.06 mg/kg. However, after the second step-up dose of 0.3 mg/kg on day 4, the patient developed grade 1 cytokine release syndrome the following day. As fever did not respond to acetaminophen, tocilizumab was administered, resulting in rapid resolution without recurrence. Immune effector cell–associated neurotoxicity syndrome did not occur during treatment.
A subcutaneous abdominal mass measuring 3.2 cm before teclistamab initiation increased to 4.4 cm on day 16 but subsequently regressed and evolved into a scar by day 52 (Fig. 1 ). By day 80, all extramedullary lesions, including the pulmonary nodules, had resolved (Fig. 2 ). At 4.5 months after teclistamab initiation, both positron emission tomography–computed tomography and 10-color multiparameter flow cytometry of the bone marrow demonstrated no detectable minimal residual disease.
During the treatment course, several adverse events were observed, including diffuse erythema involving more than 50% of the anterior chest, back, and extremities on day 66, which resolved promptly following prednisolone 10 mg/day for 5 days. Grade 3 eosinophilia developed on day 80 and also resolved with prednisolone 20 mg/day for 5 days. Reactivation of hepatitis B virus was detected on day 128, and tenofovir therapy was initiated. The patient required a total of 120 g of subcutaneous immunoglobulin replacement over 7 months for hypogammaglobulinemia. At the time of this report, seven months after teclistamab initiation, he continues therapy without evidence of relapse and remains clinically stable (Fig. 3 ).
Discussion
Pulmonary extramedullary extramedullary dissemination as the disease progresses, although pulmonary parenchymal involvement is exceedingly rare, occurring in less than 1% of patients [ 8 ]. MM with pulmonary involvement has also been reported to carry a dismal prognosis, with an estimated survival of approximately 2.8 to 4 months [ 9 ].
We reviewed previously reported cases of MM with pulmonary involvement and summarized them in Table 1 [ 9 – 16 ]. These cases collectively highlight the highly aggressive nature of this condition. For example, a 51-year-old man with light-chain MM developed bilateral hilar lymphadenopathy and multiple pulmonary nodules shortly after allogeneic stem cell transplantation. Bronchoscopic biopsy revealed plasma cell infiltration consistent with recurrent myeloma, and he died of rapidly progressive respiratory failure only 16 days after admission [ 10 ]. Another patient in his late sixties, who had previously undergone autologous transplantation and had penta-refractory disease, relapsed with massive pleural effusion and mediastinal shift due to pulmonary extramedullary involvement, clinically manifesting as tension hydrothorax. Despite intensive multi-agent chemotherapy including KD-PACE, his disease remained refractory and he transitioned to palliative care [ 9 ]. Similarly, a man in his sixties developed pulmonary disease only one year after diagnosis. Despite treatment with potent novel agents, including venetoclax, carfilzomib, and dexamethasone, his disease did not respond, his performance status declined, and he ultimately elected home hospice care [ 9 ]. In contrast, a few reports have described relatively favorable outcomes, including rapid symptomatic improvement and complete resolution of pulmonary masses following introduction of novel agents such as bortezomib [ 13 , 14 ]. These findings suggest that timely and appropriate therapeutic intervention may occasionally result in meaningful disease control. Nevertheless, pulmonary parenchymal involvement remains a major poor prognostic factor, and it still remains uncertain whether newer immunotherapies targeting BCMA or GPRC5D can substantially improve outcomes in this population.
Table 1
Summary of reported cases of multiple myeloma with pulmonary involvement
M , male; F , female; HSCT , hematopoietic stem cell transplantation; VATS , video-assisted thoracoscopic surgery; CR , complete response; VGPR , very good partial response
| Year | Age / Sex | Characteristics of pulmonary lesions | Treatment | Outcome | References |
| 2006 | 51 / M | Bilateral hilar lymphadenopathy and multiple pulmonary nodules | Supportive care for relapse after allogeneic HSCT | Died of progressive respiratory failure 16 days after admission | [ 10 – 12 ] |
| 2007 | 42 / F | Right anterior mediastinal opacity and multiple pulmonary nodular lesions | Thoracoscopic biopsy (VATS), melphalan + steroids | Symptomatic improvement after 2 months | [ 11 – 13 ] |
| 2010 | 20 / F | Solid tissue formation within cystic lung lesion | Diagnostic thoracotomy and wedge resection | Excellent prognosis after complete resection | [ 12 , 13 ] |
| 2010 | 68 / F | Solid right lower-lobe pulmonary nodule | Diagnostic thoracotomy and wedge resection | Excellent prognosis after complete resection | [ 12 – 14 ] |
| 2012 | 64 / M | Large apical lung mass (11 × 6 cm) | Bortezomib + dexamethasone | Complete disappearance; stringent CR | [ 13 – 15 ] |
| 2013 | 62 / F | Multiple bilateral non‑calcified pulmonary nodules | Bortezomib + lenalidomide + dexamethasone | Rapid radiologic resolution; sustained VGPR | [ 14 – 16 ] |
| 2022 | 65 / M | Heterogeneous pulmonary and pleural masses | Chemotherapy | Lost to follow‑up | [ 15 , 10 ] |
| 2024 | Late 60s / M | Massive pleural effusion with mediastinal shift (tension hydrothorax) | Thoracentesis, selinexor, dexamethasone | No response; progressive respiratory failure; palliation | [ 9 , 10 ] |
| 2024 | Mid‑60s / M | Pulmonary extramedullary plasmacytoma | Venetoclax + carfilzomib + dexamethasone | Clinical deterioration; home hospice | [ 9 , 17 ] |
| 2026 | 61 / M | Multiple randomly distributed pulmonary nodules with interstitial thickening | Identified during lenalidomide maintenance | Timely intervention enabled | [ 16 ] |
Extramedullary disease in MM is biologically aggressive and often resistant to conventional therapies. This is partly attributed to plasmablastic morphology or the presence of high-risk cytogenetic abnormalities such as del(17p) or 1q amplification [ 17 ]. Such cases are often resistant to standard therapies for MM, including IMiDs, PIs, and anti-CD38 antibodies. Although cytogenetic analysis of the pulmonary lesions was not feasible in our case, the absence of high-risk abnormalities in the bone marrow may have contributed to the favorable response achieved.
Radiographically, pulmonary MM lesions can present with highly variable imaging appearances, making it difficult to distinguish them from disease entities such as lymphoma, post-transplant lymphoproliferative disorder, miliary tuberculosis, metastatic tumors, or infectious pneumonia based on imaging alone [ 10 , 16 ]. A definitive diagnosis generally requires lung biopsy confirming CD138-positive plasma cells with light-chain restriction. However, in the present case, the coexistence of multiple soft-tissue extramedullary masses along with a rising IgA level strongly suggested clinical progression, leading us to initiate prompt treatment without invasive biopsy. This timely intervention may ultimately have contributed to the successful clinical outcome.
Recently, therapeutic strategies for EMD in MM have evolved with the development of bispecific antibodies. In particular, dual-targeting strategies combining BCMA- and GPRC5D-directed bispecific antibodies have shown promising efficacy, as demonstrated in the RedirecTT-1 study [ 18 ] evaluating teclistamab plus talquetamab. In this context, our case highlights that teclistamab may still achieve meaningful responses in selected patients with pulmonary extramedullary involvement.
Pseudoprogression is an important clinical consideration during treatment with immune-based therapies. In our patient, enlargement of the abdominal wall mass was observed shortly after initiation of teclistamab. In lymphoma, pseudoprogression has been documented in approximately 10–20% of patients treated with immune checkpoint inhibitors within the first 12 weeks after therapy initiation [ 19 ]. Similarly, pseudoprogression has also been reported in MM during treatment with BCMA-directed bispecific antibodies [ 20 ]. The mechanism of pseudoprogression is thought to involve rapid recruitment and accumulation of T cells within tumor lesions, along with transient cytokine-mediated inflammation. Indeed, tumor specimens from patients responding to CAR T-cell therapy have demonstrated increased infiltration of cytotoxic T cells and macrophages. Furthermore, post-treatment elevation of interleukin-8 has been proposed as a potential biomarker associated with pseudoprogression [ 21 ]. Given the biochemical improvement in M-protein levels despite apparent tumor enlargement, pseudoprogression was clinically suspected, and treatment with teclistamab was continued, leading to an excellent response. This case suggests that, when treating MM with BsAb therapy, it may be reasonable to continue treatment when clinically feasible, even if transient enlargement of some lesions is observed, provided that the overall clinical situation remains favorable.
This case represents a rare and informative clinical experience demonstrating that teclistamab can provide meaningful therapeutic benefit even in RRMM with extramedullary disease involving the lung, which is generally associated with extremely poor outcomes. Although bispecific antibodies may not always achieve high response rates in RRMM with EMD, given that treatment options for triple-class–exposed RRMM remain limited, the presence of extramedullary involvement alone should not preclude consideration of BsAb therapy. Further accumulation of large-scale real-world data specifically focusing on BsAb therapy in MM patients with pulmonary EMD will be essential to identify the clinical and biological factors that may predict therapeutic benefit.
Author contributions
TT wrote the main manuscript. KO provided patient data. All authors discussed the case and contributed to the final manuscript.
Funding
No funding was received for conducting this study.
Data availability
The data supporting the findings of this study are available upon request from the corresponding author. The data were not publicly available because of privacy or ethical restrictions.
Declarations
Consent for publication
Written informed consent for publication was obtained from the patient.
Competing interests
TT received Honoraria from Sanofi, Takeda, AbbVie, Janssen, Bristol-Myers Squibb, Chugai, Fujimoto, Kyowa Kirin, Ono, Novartis, PharmaEssentia, Meiji Seika, Genmab, research funding from GlaxoSmithKline, AbbVie, Perseus Proteomics, Pfizer, Janssen, Bristol-Myers Squibb, and consulting fees from Janssen, GlaxoSmithKline, Sanofi.MH has received Honoraria from Asahi Kasei, Nippon Shinyaku, AbbVie, Nippon Kayaku, Alexion Pharma, Chugai, Daiichi Sankyo, AstraZeneca, Otsuka, Amgen, Janssen, Novartis, Gilead Sciences, Bristol-Myers Squibb, PharmaEssentia, MSD, Kyowa Kirin, Eisai, Genmab, Argenx, Pfizer, IVF Osaka Clinic, Meiji Seika, Mallinckrodt, Abbott, H.U. FRONTIER, Osaka Medical Association, Sanofi, Ono, Astellas, research funding from Nippon Shinyaku, Labcorp, Bristol-Myers Squibb, Sumitomo, consulting fees from Kyowa Kirin, Mochida, Ono, donation from Mochida, Asahi Kasei, Japan Blood Products Organization, Otsuka, TAIHO, Chugai, Kyowa Kirin, JCR PHARMACEUTICALS, Sumitomo, Nippon Kayaku, Sekisui Medical.
Footnotes
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References
1. Gandhi UH, Cornell RF, Lakshman A et al (2019) Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia 33:2266–2275
2. Mateos MV, Weisel K, De Stefano V et al (2022) LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma. Leukemia 36:1371–1376
3. Mateos MV, Weisel K, De Stefano V et al (2024) LocoMMotion: a study of real-life current standards of care in triple-class exposed patients with relapsed/refractory multiple myeloma – 2-year follow-up (final analysis). Leukemia 38:2554–2560
4. Touzeau C, Krishnan AY, Moreau P et al (2024) Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies. Blood 144:2375–2388
5. Ishida T, Kuroda Y, Matsue K et al (2025) A Phase 1/2 study of teclistamab, a humanized BCMA × CD3 bispecific Ab in Japanese patients with relapsed/refractory MM. Int J Hematol 121:222–231
6. Tan CR, Asoori S, Huang CY et al (2025) Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study. Blood cancer J 15:53
7. Costa LJ, Bahlis NJ, Usmani SZ et al (2024) MM-328 efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma (RRMM) with high-risk (HR) features: A subgroup analysis from the phase 1/2 MajesTEC-1 study. Clin Lymphoma Myeloma Leuk 24:S546–S7
8. Kintzer JS Jr., Rosenow EC 3rd, Kyle RA (1978) Thoracic and pulmonary abnormalities in multiple myeloma. A review of 958 cases. Arch Intern Med 138:727–730
9. Kumar S, Mazloom A, Carter M, Manisha F, Polski J, Alkharabsheh O (2024) Extramedullary Pulmonary Manifestations of Relapsed/Refractory Multiple Myeloma: A Case Series and Brief Review of the Literature. J Respiration 4:177–187
10. O’Sullivan P, Müller NL (2006) Pulmonary and nodal multiple myeloma mimicking lymphoma. Br J Radiol 79:e25–e27
11. Luh SP, Lai YS, Tsai CH, Tsao TC (2007) Extramedullary plasmacytoma (EMP): Report of a case manifested as a mediastinal mass and multiple pulmonary nodules and review of literature. World J Surg Oncol 5:123
12. Huwer H, Jacobs G, Kalweit G, Püschel W (2010) Solitary pulmonary plasmacytoma: report of two cases. Med Oncol (Northwood Lond Engl) 27:59–61
13. Shah BK, Shrestha A (2012) Pulmonary plasmacytoma. J Thorac oncology: official publication Int Association Study Lung Cancer 7:923
14. Sumrall B, Diethelm L, Brown A (2013) Jr. Multiple myeloma relapse following autologous stem cell transplant presenting with diffuse pulmonary nodules. Ochsner J 13:553–557
15. Saidi I, El Idrissi Tourane LO, Ait Batahar S, Amro L (2022) A case of Multiple Myeloma with lung plasmacytoma. Respiratory Med case Rep 39:101713
16. Kumar A, Raj G, Gupta K et al (2026) Disseminated pulmonary involvement in multiple myeloma: A rare extramedullary manifestation on CT. Radiol case Rep 21:748–751
17. Bladé J, Beksac M, Caers J et al (2022) Extramedullary disease in multiple myeloma: a systematic literature review. Blood cancer J 12:45
18. Kumar S, Mateos MV, Ye JC et al (2026) Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab. N Engl J Med 394:51–61
19. Lee AJ, Kim KW, Cho YC et al (2021) Incidence of immune-mediated pseudoprogression of lymphoma treated with immune checkpoint inhibitors: systematic review and meta-analysis. J Clin Med 10:2257
20. Khan AM, Kroog GS, Roccia T, Knorr K, Boyapati A, Bumma N (2025) Radiologic pseudoprogression associated with a positive response in a patient with multiple myeloma treated with a BCMA×CD3 bispecific antibody: a case report. EJHaem 6:e70168
21. DeanEA (2026) CAR T-cell therapy induced pseudoprogression. Front Immunol 17:1691562. 10.3389/fimmu.2026.1691562
Associated Data
Data Availability Statement
The data supporting the findings of this study are available upon request from the corresponding author. The data were not publicly available because of privacy or ethical restrictions.