Visual Summary Teclistamab Enables Heart Transplantation in AL Cardiac Amyloidosis AL = immunoglobulin light chain amyloid; BCMA = B-cell maturation antigen; CR = complete response; Dara-CyBorD = daratumumab, cyclophosphamide, bortezomib, and dexamethasone; MRD = minimal residual disease.
Immunoglobulin light chain amyloid (AL) cardiomyopathy is the most aggressive form of amyloid heart disease with high morbidity and mortality. 1 The survival and outcomes of patients with AL amyloidosis are heavily dependent on the hematologic disease control and organ-directed supportive care. Achieving at least a very good partial remission, a reduction of pathogenic light chains by 90% from baseline, is critical for organ function improvement and is the desired goal of systemic therapy. 1 , 2 Daratumumab- and bortezomib-based multidrug antineoplastic therapies form the backbone of current standard of care and achieve desired hematologic response in approximately 70% of patients, translating into organ improvement for 50% of patients. 2 , 3 The outcomes for patients with progressive cardiac dysfunction are dismal, and advanced therapies such as heart transplantation (HT) are the only lifesaving intervention for such patients. 4 Adequate hematologic disease control is critical for patients with AL amyloidosis to be considered for HT. 4 Here, we report the case of a patient with highly advanced AL cardiomyopathy with hematologic disease refractory to currently available standard therapies who was able to achieve complete hematologic response with a bispecific T-cell engaging antibody, teclistamab, and underwent successful HT. Take-Home Message • Teclistamab achieved a rapid minimal residual disease–negative complete response within weeks, demonstrating its potential as a fast-acting salvage therapy capable of restoring heart transplant eligibility in advanced cardiac AL amyloidosis.
Case Presentation
A 37-year-old woman presented with new-onset nausea, abdominal pain, dyspnea, orthopnea, and bilateral lower-extremity edema. A transthoracic echocardiogram showed a severely increased concentric left ventricular wall thickness with a septal wall thickness of 20 mm, a posterior wall thickness of 17 mm, a reduced left ventricular ejection fraction of 38%, severe diastolic dysfunction, and a global average longitudinal peak systolic strain of −4% (normal = more negative than −18%) with an apical sparing pattern. Cardiac magnetic resonance confirmed diffuse subendocardial late gadolinium enhancement consistent with infiltrative cardiomyopathy. Laboratory evaluation revealed a markedly elevated serum free kappa light chain (KLC) level of 543 mg/L at initial diagnosis, which subsequently increased to a peak of 642 mg/L before therapy initiation, with a kappa/lambda (K/L) ratio of 271.5 and no detectable M-spike on serum protein electrophoresis. Bone marrow biopsy demonstrated 30% clonal plasma cells harboring a t(11;14) translocation. The patient subsequently underwent endomyocardial biopsy demonstrating Congo-red–positive deposits, and mass spectrometry confirmed AL kappa type ( Figure 1 ). Whole-body positron emission tomography/computed tomography demonstrated physiological tracer distribution without hypermetabolic lymphadenopathy, normal fluorodeoxyglucose uptake throughout the axial and appendicular skeleton, and no definitive fluorodeoxyglucose-avid osseous lesions or computed tomography–evident lytic lesions, supporting a diagnosis of systemic AL amyloidosis without overt multiple myeloma. There was no clinical or objective evidence of extracardiac amyloid involvement, including gastrointestinal or neurologic disease, that would contraindicate HT. The baseline N-terminal pro–B-type natriuretic peptide (NT-proBNP) level was 3,236 pg/mL and the high-sensitivity troponin T level was 42 ng/L, consistent with Mayo stage IIIA/European stage IV disease. Figure 1 Pretransplant Endomyocardial Biopsy Demonstrating AL Amyloid Deposition Hematoxylin and eosin staining reveals extensive pericellular and interstitial amyloid deposition producing myocyte distortion and separation. Scattered inflammatory cells are present within the interstitium. The inset highlights Congo-red–positive, congophilic amyloid deposits within the vascular wall, supporting the diagnosis of light chain amyloidosis before heart transplantation. AL = immunoglobulin light chain amyloid.
She was started on standard treatment with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. After 3 cycles, the KLC level decreased from 642 to 144 mg/L, the NT-proBNP level improved from 3,236 to 1,672 pg/mL, and the response plateaued.
Because she did not achieve an optimal response, salvage treatment with oral venetoclax, a small-molecule BCL-2 inhibitor, was initiated given her t(11;14) cytogenetic profile. She had early response to venetoclax with 40% reduction in serum KLC but had progressive worsening of nausea and gastrointestinal symptoms and could not tolerate venetoclax therapy. While undergoing evaluation of her gastrointestinal symptoms, her heart failure progressed rapidly requiring prolonged hospitalization for intravenous diuretic therapy. The hemodynamic evaluation revealed low-output heart failure (Stevenson profile C), and she was started on a continuous dobutamine drip. During this time, her plasma cell dyscrasia progressed. A multidisciplinary amyloidosis committee recommended salvage therapy to control the plasma cell dyscrasia followed by HT in accordance with the Mayo Clinic consensus recommendations for HT in amyloid cardiomyopathy. 5
Taking into account her rapidly progressive disease and refractory plasma cell dyscrasia, treatment with teclistamab, a B-cell maturation antigen (BCMA)–directed bispecific antibody, was initiated based on extrapolation from its demonstrated efficacy in relapsed and refractory multiple myeloma and accumulating evidence of efficacy in AL amyloidosis. 6 Teclistamab was administered subcutaneously using the standard step-up regimen: 0.06 mg/kg on day 1 (after dexamethasone 10 mg intravenous premedication), followed by 0.3 mg/kg on day 4 and 1.5 mg/kg on day 7, and then continued 1.5 mg/kg weekly thereafter. The therapy was well tolerated without cytokine release syndrome or neurotoxicity, despite ongoing inotrope dependence.
Serial free light chain monitoring demonstrated a rapid decline in KLC from 37 mg/L on day 2 to 8 mg/L by day 10, with normalization of the K/L ratio to <2. A bone marrow biopsy performed approximately 2 weeks after teclistamab initiation showed normocellular marrow with trilineage hematopoiesis and no morphologic or flow cytometric evidence of residual plasma cell dyscrasia, confirming minimal residual disease (MRD)–negative complete response.
During inpatient therapy, she experienced a brief episode of cardiac arrest secondary to transient hypotension and pulseless electrical activity in the setting of advanced heart failure, which was promptly reversed with cardiopulmonary resuscitation. This event was not attributed to teclistamab treatment. She recovered fully, and no recurrent arrhythmias or immune effector–related events occurred.
With hematologic remission established, she proceeded to HT within the same hospitalization. Evaluation of the explanted heart confirmed both residual amyloid and nascent fibrosis, suggesting remitting deposits ( Figure 2 ). Induction immunosuppression was omitted because of recent T-cell–redirecting therapy. Post-transplant maintenance immunosuppression included tacrolimus, mycophenolate mofetil, and a rapid prednisone taper, with infection prophylaxis and monthly intravenous immunoglobulin for teclistamab-associated hypogammaglobulinemia. She was successfully weaned from inotropes, transitioned to oral bumetanide 2 mg daily, and discharged home hemodynamically stable. Figure 2 Explanted Heart With Advanced Cardiac Amyloidosis Gross examination of the explanted heart demonstrates marked concentric myocardial thickening, particularly involving the left ventricular wall and interventricular septum, consistent with advanced infiltrative cardiomyopathy due to immunoglobulin light chain amyloid deposition.
At early post-transplant follow-up, she remained asymptomatic with normal graft function, an NT-proBNP level of <500 pg/mL, a serum creatinine level of 1.28 mg/dL, and a KLC level of 1.76 mg/L with a normalized K/L ratio, consistent with sustained MRD-negative remission. Three months after transplant, she is currently doing well with sustained hematologic response and no signs of relapse or organ rejection.
This case demonstrates that off-label teclistamab, administered with multidisciplinary inpatient monitoring, can achieve a rapid, deep hematologic response in refractory AL cardiac amyloidosis, thereby restoring eligibility for HT in an otherwise ineligible patient.
Discussion
The management of relapsed or refractory AL amyloidosis remains a significant clinical challenge, particularly in patients with advanced cardiac involvement who have exhausted standard plasma cell–directed therapies. 1 , 3 Daratumumab-based regimens remain the current standard; however, a substantial proportion of patients develop refractory disease or relapse, and those with progressive cardiac dysfunction often lack the time or physiological reserve required for slower-acting salvage strategies. 1 , 2 , 3 Adequate hematologic disease control is essential for consideration of advanced cardiac therapies, including HT, and remains the primary determinant of post-transplant outcomes. 1 , 4 , 5
The Mayo Clinic consensus statement emphasizes that HT in AL amyloidosis is feasible when deep and sustained hematologic remission is achieved, with long-term survival comparable to that of nonamyloid transplant recipients. 5 Importantly, transplant eligibility is determined by disease biology and response rather than the specific therapeutic modality used to achieve plasma cell suppression. 5 In this framework, achieving a profound hematologic response represents the critical prerequisite for successful organ-directed intervention.
Although deep hematologic remission is generally required before transplantation, some patients with rapidly progressive cardiac AL amyloidosis may not survive long enough to achieve very good partial remission. In select cases, individualized consideration of transplantation in hemodynamically unstable patients may be reasonable, particularly in the context of rapidly acting emerging plasma cell–directed therapies. This case highlights the narrow therapeutic window that can exist in advanced cardiac AL amyloidosis.
BCMA is overexpressed on clonal plasma cells in multiple myeloma and AL amyloidosis, providing an attractive target for novel immunotherapies. 7 Bispecific antibodies such as teclistamab and elranatamab, as well as chimeric antigen receptor T-cell therapies, have demonstrated efficacy in multiple myeloma and are now being explored in AL amyloidosis. 7 , 8 , 9 , 10 In the pivotal MajesTEC-1 trial, teclistamab achieved an overall response rate of 63% and a complete response rate of 39% in heavily pretreated multiple myeloma, with a median progression-free survival of 11.3 months; these results have led to its Food and Drug Administration approval for relapsed/refractory myeloma after at least 4 prior lines of therapy. 8 Early emerging evidence from case reports and small institutional experiences suggests that teclistamab can induce rapid reductions in pathogenic light chains and, in some patients, improvements in cardiac biomarkers or organ function in relapsed or refractory AL amyloidosis. 9 Elranatamab has also demonstrated a 100% overall response rate and a 67% complete response rate in advanced AL amyloidosis, with deep suppression of pathogenic light chains and organ improvement within 1 cycle. 10 These findings support the concept that BCMA-directed bispecific antibodies can achieve the depth and speed of hematologic response required in patients with aggressive disease and advanced organ involvement.
The safety profile of teclistamab is generally manageable, with most adverse events being low grade and reversible, including cytokine release syndrome and cytopenias, although infections and immune effector cell–associated neurotoxicity can occur and warrant close monitoring. 7 , 8 Anti-BCMA CAR T-cell therapy has demonstrated high hematologic response rates and organ recovery in AL amyloidosis; however, toxicity, manufacturing timelines, and early mortality in patients with advanced cardiac disease limit its applicability in frail populations. 11 In contrast, the off-the-shelf availability and rapid onset of action of BCMA-directed bispecific antibodies such as teclistamab provide a practical advantage in patients with rapidly progressive disease and limited physiological reserve. 1 , 9
In this case, teclistamab induced an MRD-negative complete hematologic response within 2 weeks, with normalization of free light chains and clearance of clonal plasma cells, despite severe, inotrope-dependent heart failure. This depth of hematologic response restored eligibility for HT, which was successfully performed during the same hospitalization, and the patient remained in hematologic remission at early follow-up. Together, these findings reinforce that achievement of profound plasma cell suppression, rather than reliance on a specific therapeutic agent, is critical for transplant candidacy and outcomes in AL amyloidosis, consistent with contemporary consensus recommendations. 5 , 9
Because the therapeutic landscape continues to evolve, BCMA-directed therapies, including teclistamab and elranatamab, and CAR T-cell constructs are likely to further expand treatment options for patients with relapsed or refractory AL amyloidosis. Ongoing challenges include defining optimal patient selection, timing relative to transplant evaluation, infectious risk associated with sustained immunosuppression, and optimal sequencing of BCMA-directed agents. 10 , 11
Conclusions
Teclistamab enabled rapid, deep hematologic response and successful organ transplantation in a patient with refractory cardiac AL amyloidosis, demonstrating the promise of BCMA-directed bispecific antibodies in this challenging context. 8 These agents offer a novel, effective option for relapsed/refractory AL amyloidosis, but further prospective studies are needed to define patient selection, timing, and management of associated toxicities. 1 , 4 , 7 , 10 Multidisciplinary care and vigilant monitoring remain essential to optimize outcomes in this vulnerable population. 8 , 9 , 10 , 11
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
References
1 Sanchorawala V. Systemic light chain amyloidosis N Engl J Med 390 2024 2295 2307 38924733 10.1056/NEJMra2304088
2 Palladini G. Milani P. Merlini G. Management of AL amyloidosis in 2020 Blood 136 23 2020 2620 2627 33270858 10.1182/blood.2020006913
3 Kastritis E. Palladini G. Minnema M.C. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis N Engl J Med 385 2021 46 58 34192431 10.1056/NEJMoa2028631
4 Patel J. Kobashigawa J. Kittleson M. Cardiac transplantation in light-chain amyloidosis: outcomes in the contemporary era J Heart Lung Transpl 40 2021 763 771
5 Lyle M. Rosenthal J. Nativi Nicolau J. Heart transplantation for cardiac amyloidosis: Mayo Clinic consensus statement Mayo Clin Proc 100 9 2025 1578 1605 40767789 10.1016/j.mayocp.2025.05.009
6 Leung N. Chapman J.A. Bhatia S. First report of teclistamab in a patient with relapsed AL amyloidosis and multiple myeloma EJHaem 4 4 2023 1157 1159 10.1002/jha2.772 38024617 PMC10660095
7 Jamroziak K. Zielonka K. Khwaja J. Wechalekar A.D. Update on BCMA-directed therapies in AL amyloidosis Br J Haematol 206 2025 817 831 39748220 10.1111/bjh.19960
8 Moreau P. Garfall A.L. van de Donk N. Teclistamab in relapsed or refractory multiple myeloma N Engl J Med 387 2022 495 505 35661166 10.1056/NEJMoa2203478 PMC10587778
9 Chen Z. Zhang Z. Yu J. Teclistamab in relapsed/refractory amyloidosis (case series) Front Oncol 15 2025 1664171 10.3389/fonc.2025.1664171 PMC12488438 41049832
10 Vianna P.G. Chakraborty R. Hossain S. Elranatamab in relapsed and refractory AL amyloidosis Blood 146 2025 1929 1935 40712156 10.1182/blood.2025028383 PMC12757077
11 Lebel E. Asherie N. Kfir-Erenfeld S. BCMA CAR T-cell therapy in relapsed AL amyloidosis: updated experience J Clin Oncol 43 2025 2007 2016 39653116 10.1200/JCO-24-02252
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center .