Multiple myeloma accounts for approximately 10 percent of hematological cancers in the United States, and there is currently no cure.

 There is a need for additional treatments as most patients with multiple myeloma will relapse or become refractory to treatment.

 In recent years, there have been a growing number of therapies, including B-cell maturation antigen (BCMA)-targeting agents, available for patients with advanced disease.

 BCMA antigen is overexpressed in multiple myeloma cells, and therapies targeting this antigen have shown efficacy in the treatment of multiple myeloma over the past decade.

 (teclistamab-cqyv) was approved in the United States in October 2022 for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM), who previously received at least four or more prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.

 This indication is approved under accelerated approval based on response rate.

 Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

The approval is based on the pivotal Phase 1 / Phase 2 MajesTEC-1 study (detailed below) which evaluated adults with relapsed or refractory multiple myeloma.

 is the first bispecific antibody treatment approved in multiple myeloma. It’s imperative to continue to collaborate and broaden the treatment landscape to provide additional options to patients who are in need,” said Emma Searle, M.D., Ph.D., consultant hematologist, Christie Hospital NHS Foundation Trust. “TECVAYLI

 is an off-the-shelf therapy and the first BCMA bispecific therapy in relapsed or refractory myeloma, providing physicians with an important subcutaneous option for patients.”

 is a bispecific T-cell engager antibody therapy which uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T cells and to the BCMA expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.

 is a subcutaneous injection which is administered by a healthcare provider. It is available in two vial sizes with different concentrations: a 30 mg / 3mL single-use vial used during the step-up doses and a 153 mg / 1.7 mL single-use treatment vial.

“As a clinician, I see the needs of patients and how many are eagerly awaiting new therapies. Patients who are looking for new options and new hope are what drives our passion to focus on areas in oncology with high unmet need to bring therapies to physicians who are on the front line of treating blood cancers,” said Imran Khan, M.D., Ph.D., Vice President, US Hematology Medical Affairs, Janssen. “TECVAYLI

 is the fourth Janssen therapy approved in multiple myeloma, underscoring our experience in treating this disease, and also our commitment to the patients who are eagerly awaiting additional options.”

 includes a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell–associated neurotoxicity (ICANS).

 is available only through a Risk Evaluation and Mitigation Strategy (REMS) program.

 The REMS program is in place to help inform prescribers of known or potential serious risks associated with the treatment and ensure the benefits outweigh potential risks of CRS or neurologic toxicities, including ICANS.

 Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the TECVAYLI

 was evaluated in a single-arm, open-label, multi-center study (MajesTEC-1, 

 [Phase 2]). The study included patients who had previously received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

 Patients received step-up doses of 0.06 mg/kg and 0.3 mg/kg of TECVAYLI

 1.5 mg/kg, subcutaneously once weekly (N=165).

Results: An overall response rate (ORR) of 61.8 percent (n=68/110; 95 percent. Confidence Interval [CI]: 52.1 percent, 70.9 percent) was achieved, notably with 28.2 percent of patients achieving a complete response (CR) or better (n=31/110; CR or better equals stringent complete response [sCR] plus CR).

 Efficacy was established based on ORR (ORR equals sCR, CR, very good partial response and partial response combined) as determined by the Independent Review Committee (IRC) assessment using International Myeloma Working Group (IMWG) 2016 criteria.

Median time to first response was 1.2 months (range 0.2 to 5.5 months)

With a median follow-up of 7.4 months among responders, the estimated duration of response (DOR) rate was 90.6 percent (95 percent CI: 80.3 percent, 95.7 percent) at six months and 66.5 percent (95 percent CI: 38.8 percent, 83.9 percent) at nine months. The estimated duration of response (DOR) rate was not yet reached

Seventy-eight percent of patients received at least four prior lines of therapy

All patients had received prior therapy with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

In addition to the Boxed Warning for CRS, neurologic toxicity including ICANS, and the REMS program noted above, Warnings and Precautions for TECVAYLI

 include: hepatotoxicity, infections, neutropenia, hypersensitivity and other administration reactions, and embryo-fetal toxicity

Most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea

Most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin and decreased platelets

Please see below for full Important Safety Information

 may be a great choice for patients and a huge step forward for the myeloma community as it offers another option to patients who are highly relapsed or refractory. I am optimistic for the future of multiple myeloma treatment, that this changing landscape will continue to provide options to our patients, providers and loved ones in the community,” said Searle.

 (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI

 step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI

 until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI

. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI

until neurologic toxicity resolves or permanently discontinue based on severity.

 is available only through a restricted program called the TECVAYLI

 and TALVEY™ Risk Evaluation and Mitigation Strategy (REMS).

 can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI® at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI

. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).

 step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI

 accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI

 is available only through a restricted program under a REMS.

 can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI

 at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI

In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI

 at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI

. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI

 based on severity per recommendations and consider further management per current practice guidelines.

Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI

 step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

 is available only through a restricted program under a REMS called the TECVAYLI

 REMS because of the risks of CRS and neurologic toxicity, including ICANS.

 can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI

 at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI

 or consider permanent discontinuation of TECVAYLI

 can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI® at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%. Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI

and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Withhold TECVAYLI® or consider permanent discontinuation of TECVAYLI

Monitor immunoglobulin levels during treatment with TECVAYLI

 and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

 can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI

 at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.

Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI

Hypersensitivity and Other Administration Reactions - 

 can cause both systemic administration-related and local injection-site reactions. 

 - In patients who received TECVAYLI® at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. 

 at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI

 Based on its mechanism of action, TECVAYLI

 may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI

The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%)were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Wu L, Huang Y, Sienkiewicz J, Sun J, Guiang L, Li F, et al. Bispecific BCMA-CD3 antibodies block multiple myeloma tumor growth. 

. 2022; 14(10). https://doi.org/10.3390/cancers14102518

Dhodapkar MV, Borello I, Cohen A, Stadtmauer MD. Hematologic malignancies: plasma cell disorders. 

 2022; 23(3):1649. doi:10.3390/ijms23031649

Das S, Juliana N, Yazit NAA, Azmani S, Abu IF. Multiple myeloma: challenges encountered and future options for better treatment. 

Kleber M, Ntanasis-Stathopoulos I, Terpos E. BCMA in multiple myeloma-a promising key to therapy. 

. 2021;10(18):4088. Published 2021 Sep 10. doi:10.3390/jcm10184088

Kumar S, Rajkumar V, Kyle R, et al. Multiple myeloma. 

2017;3:17046. https://doi.org/10.1038/nrdp.2017.46

 [Prescribing Information]. Janssen Biotech, Inc.

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