Two-Drug Combination Shows Strong Results in Hard-to-Treat Extramedullary Myeloma

Table of Contents

• Key Points
• Understanding Extramedullary Myeloma
• Why Target Two Antigens at Once?
• How the Study Was Designed
• Who Was in the Study
• Key Findings: Response Rates
• Duration of Response and Survival
• Side Effects and Safety Profile
• What This Means for Patients
• Limitations of the Study
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• In a phase 2 study of 90 patients, talquetamab plus teclistamab led to a response in 79% and complete response or better in 54%.
• The median duration of response was 13.8 months, and 74% of patients were alive at 12 months.
• Responses occurred in 83% of patients who had prior CAR-T therapy, suggesting dual targeting can overcome resistance.
• Common side effects included oral symptoms (87%), cytokine release syndrome (78%), and severe infections (31%).
• Most responders (77%) switched to monthly dosing, and 93% of those maintained or deepened their response.

Understanding Extramedullary Myeloma

Multiple myeloma is a cancer of plasma cells, a type of white blood cell normally found in the bone marrow. In most patients, the disease stays within the bone marrow. But in some patients, the cancer forms tumors called plasmacytomas outside the bone marrow entirely. Doctors call this "true extramedullary myeloma." These tumors are not connected to bone and do not disrupt the bone cortex (the hard outer layer of bone).

True extramedullary disease is a high-risk feature. It is linked to treatment resistance and the ability of cancer cells to evade apoptosis (programmed cell death, a natural process by which damaged cells normally destroy themselves).

How common is this condition? At the time of diagnosis, approximately 0.5 to 5.2% of myeloma patients have true extramedullary disease. That percentage rises to 3.4 to 14.0% in patients whose disease has relapsed (returned after treatment) or become refractory (stopped responding to treatment).

Outcomes for these patients are poor. In a prospective, noninterventional study, patients with extramedullary myeloma treated with standard therapies had a median overall survival (the time from treatment until death from any cause) of 7.2 months and a median progression-free survival (the time until the disease worsens or the patient dies) of just 2.6 months.

A meta-analysis (a statistical analysis that combines results from multiple studies) found that patients with true extramedullary myeloma were 87% less likely to respond to treatment compared with patients without extramedullary disease. They were also approximately twice as likely to have disease progression or to die. Despite these grim numbers, few large prospective interventional studies have focused specifically on this patient population — which is exactly what the RedirecTT-1 study set out to do.

Why Target Two Antigens at Once?

Plasmacytomas are complex tumors. They show high genomic variety (differences in the DNA of the cancer cells) and a complex microenvironment (the surrounding tissues and cells that support tumor growth). Critically, they have heterogeneous (uneven) expression of two important proteins on their surface: GPRC5D (G protein–coupled receptor family C group 5 member D) and BCMA (B-cell maturation antigen). Some cancer cells may have GPRC5D but not BCMA, or vice versa — which is why targeting only one protein may allow the cancer to escape.

Talquetamab is a bispecific antibody that targets GPRC5D. Teclistamab is a bispecific antibody that targets BCMA. Both are "first-in-class" drugs — the first of their kind — approved as monotherapies (single-drug treatments) for relapsed or refractory myeloma in patients who have previously been exposed to three classes of treatment: a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody (collectively known as "triple-class exposure").

The rationale for combining them is simple: hitting two different targets on the cancer cells at once may produce deeper and more durable responses than hitting either target alone. Evidence from the phase 1 portion of the RedirecTT-1 study supported this idea. In that earlier phase, the recommended phase 2 regimen of talquetamab plus teclistamab produced a response in 80% of patients, with a complete response or stringent complete response in 52%, and a 91% probability of maintaining the response for at least 12 months.

Especially relevant: in the subgroup of phase 1 patients with true extramedullary myeloma, a response occurred in 61%, and the probability of a 12-month duration of response was 82%. The safety profile was consistent with what is seen with each drug used alone. The phase 2 portion of the study — the focus of this article — was designed to test this dual-targeting approach specifically and exclusively in patients with true extramedullary myeloma.

How the Study Was Designed

The RedirecTT-1 study is a multicenter (conducted at many sites), nonrandomized (all patients received the same treatment), open-label (both patients and doctors knew which drugs were given) phase 1b–2 study of talquetamab plus teclistamab.

For the phase 2 cohort, patients had to have true extramedullary myeloma. This was strictly defined: at least one nonradiated, bone-independent (not connected to bone), soft-tissue plasmacytoma measuring 2 cm or more in its greatest dimension. The tumor had to be confirmed by central review of whole-body PET-CT scans (positron-emission tomography combined with computed tomography, a scan that shows both the location and metabolic activity of tumors). MRI (magnetic resonance imaging) was permitted as an alternative to PET-CT with sponsor approval.

Patients with paramedullary plasmacytomas (tumors connected to bone that extend into soft tissue after breaking through the bone cortex) were eligible if they also had true extramedullary disease. But patients with only paramedullary tumors, central nervous system involvement, or plasma-cell leukemia were excluded. All patients had confirmed myeloma according to IMWG (International Myeloma Working Group) criteria. Patients with nonsecretory disease (myeloma that does not produce a measurable M-protein in blood or urine) or oligosecretory disease (producing very low levels of M-protein) were permitted.

Eligible patients had disease that was in relapse or refractory to one or more established therapies — including the most recent line of therapy — or had discontinued treatment because of unacceptable side effects. All patients had previous triple-class exposure (meaning they had already tried a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody).

Patients could not receive radiation therapy beyond the end of cycle 2 unless the sponsor approved it, to ensure response evaluation was not affected. Patients who had previously received CAR-T therapy (chimeric antigen receptor T-cell therapy, a treatment that genetically engineers the patient's own immune cells to attack cancer) were allowed if the therapy-free interval was more than 3 months. Enrollment of these patients was limited to 20% of the study population. Prior treatment with bispecific antibodies was allowed with a therapy-free interval of more than 21 days, but the prior bispecific antibodies could not target GPRC5D or BCMA. Previous use of belantamab mafodotin (a BCMA-targeted antibody-drug conjugate) was permitted.

The study was designed by Johnson & Johnson, the sponsor. It was conducted according to the principles of the Declaration of Helsinki and the International Council for Harmonisation guidelines for Good Clinical Practice. Each site's institutional review board approved the protocol, and all patients gave written informed consent.

Dosing and Treatment Schedule

Patients received talquetamab subcutaneously (under the skin) at a dose of 0.8 mg per kilogram of body weight, plus teclistamab at a dose of 3.0 mg per kilogram, every other week in 28-day cycles. Before the full doses began, there was a step-up period with gradually increasing doses, adapted from the approved schedules used with each drug as monotherapy.

Both drugs were given on the same day, 30 (±10) minutes apart, for all step-up and full treatment doses. After completing four cycles with a very good partial response or better — or after six cycles regardless of response depth — patients could switch to monthly dosing at the investigator's discretion.

Patients stayed on treatment until unacceptable side effects developed, consent was withdrawn, disease progression was confirmed, death occurred, or the investigator or sponsor decided to stop treatment.

End Points and Response Assessment

The primary end point (the main question the study was designed to answer) was overall response, defined as a partial response or better. Responses were assessed by an independent review committee using IMWG 2016 criteria, plus independent central radiology review of whole-body FDG PET-CT scans (a scan using a radioactive sugar tracer, 18F-fluorodeoxyglucose, to find metabolically active cancer cells) or diffusion-weighted whole-body MRI.

Because the IMWG criteria do not include PET-CT–specific response criteria, the study team adapted them to assess extramedullary myeloma response. PET results were interpreted using the Deauville score (a 1 to 5 scale, with higher scores indicating greater FDG uptake, meaning more active cancer) and Italian myeloma criteria for PET use (IMPETUS).

Response definitions were detailed and imaging-based:

• Complete response: Disappearance of all plasmacytomas, or persistence of fibrotic (scar-like) disease with a Deauville score of 1 to 3.
• Stringent complete response: Complete response plus a normal free-light-chain ratio (a blood test measuring antibody fragments) and no clonal plasma cells (cancerous cells that are all descendants of one abnormal cell) on biopsy.
• Very good partial response: At least 90% size reduction in all plasmacytomas and reduced FDG avidity (lower tracer uptake) from baseline.
• Partial response: At least 50% size reduction in all plasmacytomas and reduced FDG avidity from baseline.

Secondary end points included time to response, very good partial response or better, complete response or better (complete response or stringent complete response), stringent complete response, duration of response, progression-free survival, overall survival, and safety.

Side effects were graded using the Common Terminology Criteria for Adverse Events, version 5.0, and were recorded up to 30 days after the last dose or until the start of a new antimyeloma therapy. Cytokine release syndrome (a widespread inflammatory reaction caused by the immune system's response to the treatment) and ICANS (immune effector cell–associated neurotoxicity syndrome, a neurological side effect involving confusion or brain dysfunction) were graded using guidelines from the American Society for Transplantation and Cellular Therapy.

Statistical Design

The study was designed to test the hypothesis that the combination would have significant antimyeloma activity in true extramedullary disease. The null hypothesis (the assumption that the treatment does not work) would be rejected if the lower bound of the 95% confidence interval exceeded 40%. The sample size provided 96% power to test this hypothesis. Data were analyzed with SAS software, version 9.4. Confidence intervals were not adjusted for multiplicity, so they should not be used to infer definitive treatment effects for the secondary end points.

Who Was in the Study

Between July 5, 2023, and September 16, 2024, a total of 132 patients were screened for the study. Of those, 42 were excluded: 35 did not meet eligibility criteria, and 7 withdrew consent.

That left 90 patients with extramedullary myeloma who received the study treatment. The median follow-up was 12.6 months (range, 0.5 to 19.5 months). As of the data cutoff date of March 18, 2025, 49 patients (54%) were still receiving treatment, including 2 patients receiving only teclistamab after stopping talquetamab due to side effects.

Of the 41 patients who discontinued both drugs: 27 had progressive disease (the cancer worsened), 9 had an adverse event, 3 withdrew, and 2 were withdrawn by their physician.

Key patient characteristics at baseline:

• Median age: 64.5 years
• Median previous lines of treatment: 4 (range, 1 to 10); 43% had 3 or fewer, and 57% had more than 3
• Median time since diagnosis: 4.7 years (range, 0.7 to 21.4)
• Median number of extramedullary disease sites: 2 (range, 1 to 7); 42% had 1 site, 32% had 2 to 3 sites, and 26% had 4 or more sites
• 60% had at least one soft-tissue site, 39% had at least one lymph-node site, and 33% had at least one organ site
• Most common disease sites: retroperitoneum (the area behind the abdominal cavity), abdominal wall, and chest wall
• 19 patients (21%) also had paramedullary sites alongside the true extramedullary disease
• Tumor volume: less than 25 cm² in 49 patients (54%), 25 to 50 cm² in 19 patients (21%), and more than 50 cm² in 22 patients (24%)
• Nonsecretory disease: 4 patients (4%); oligosecretory disease: 31 patients (34%)
• Bone marrow plasma cells 60% or more: 10 of 86 patients (12%)
• High cytogenetic risk (chromosome abnormalities del[17p], t[4;14], or t[14;16]): 14 of 65 patients (22%)

Importantly for understanding how this treatment fits into the treatment landscape: 18 patients (20%) had previously received anti-BCMA CAR-T therapy, and 8 patients (9%) had previously received bispecific antibodies (all targeting Fc receptor homologue 5, a different target). The median time from CAR-T therapy to the start of the study treatment was 295 days (range, 98 to 1,030 days).

These characteristics were generally representative of the overall population of patients with relapsed or refractory extramedullary myeloma.

Key Findings: Response Rates

The central finding is strong: a response occurred in 71 of 90 patients — 79% (95% confidence interval [CI], 69 to 87). In plain terms, about 8 in 10 patients responded.

That result substantially exceeded the pre-specified threshold of 40%, meaning the study's primary hypothesis was met with statistical significance. A confidence interval this wide (69 to 87) reflects the uncertainty inherent in a study of 90 patients, but even the lower bound is far above the 40% threshold.

Deeper responses were also common:

• Very good partial response or better: 63 patients (70%; 95% CI, 59 to 79) — about 7 in 10
• Complete response or better: 49 patients (54%; 95% CI, 44 to 65) — about 5 in 10

The median time to first response was 2.6 months (range, 1.0 to 5.8 months), and the median time to best response was 4.7 months (range, 1.0 to 11.9 months). This means most patients who were going to respond did so fairly quickly, though some took up to nearly a year to reach their best response.

Responses in Hard-to-Treat Subgroups

Responses were similar across clinically relevant subgroups, including patients with more than three prior lines of therapy, International Staging System stage III myeloma (advanced disease), four or more extramedullary sites at baseline, or high-risk cytogenetics.

Patients with organ disease sites (tumors involving internal organs) had a response rate of 83% (95% CI, 65 to 94), while patients with nonorgan sites had a response rate of 77% (95% CI, 64 to 87).

Tumor volume mattered somewhat, though responses were good across all categories:

• Tumor volume less than 25 cm²: 82% response (95% CI, 68 to 91)
• Tumor volume 25 to 50 cm²: 74% response (95% CI, 49 to 91)
• Tumor volume greater than 50 cm²: 77% response (95% CI, 55 to 92)

Patients with Prior CAR-T or Bispecific Therapy

One of the most clinically relevant questions is whether this combination works after other modern treatments have failed. The results are encouraging.

Among the 18 patients who had previously received anti-BCMA CAR-T therapy:

• 15 patients (83%; 95% CI, 59 to 96) achieved a very good partial response or better
• 14 patients (78%; 95% CI, 52 to 94) achieved a complete response or better

Among the 8 patients who had previously received bispecific antibody therapy (all targeting Fc receptor homologue 5, not GPRC5D or BCMA):

• 6 patients (75%; 95% CI, 35 to 97) had a response
• 5 patients (62%; 95% CI, 24 to 91) had a very good partial response or better
• 3 patients (38%; 95% CI, 8 to 76) had a complete response or better

Duration of Response and Survival

Responses were not only frequent — they were also durable.

The median duration of response (the time from the first response until the disease progresses or death) was 13.8 months (95% CI, 11.5 to not estimable). Among patients who responded, 64% (95% CI, 48 to 76) had a response lasting at least 12 months.

In the subgroup with prior CAR-T therapy, the median response duration was also 13.8 months, with 72% (95% CI, 41 to 89) maintaining a response for at least 12 months.

At the time of the data cutoff, 66% of patients who had responded were still receiving study treatment, with a median follow-up of 13.4 months (range, 1.2 to 19.5).

Of the 71 patients who responded, 55 (77%) switched to monthly dosing. Most of those responses (51 of 55, or 93%) either deepened or were maintained in the first 6 months after the switch — evidence that the monthly schedule was not only convenient but effective.

Survival metrics were also encouraging for this high-risk population:

• Median progression-free survival: 15.4 months (95% CI, 10.8 to not estimable). In other words, half of the patients had not experienced disease progression or death at 15.4 months.
• 12-month progression-free survival: 61% (95% CI, 50 to 71) — about 6 in 10 patients
• 12-month overall survival: 74% (95% CI, 63 to 83) — about 7 in 10 patients

For context, recall that in the earlier observational study of standard therapies in extramedullary myeloma, median progression-free survival was only 2.6 months and median overall survival was only 7.2 months. Direct comparisons across different studies should be made cautiously, but the contrast is striking.

Side Effects and Safety Profile

With powerful treatments come side effects, and the safety profile of this combination deserves careful attention.

The most common adverse events of any grade were:

• Oral symptoms — including dysgeusia (taste changes), dry mouth, and dysphagia (difficulty swallowing): occurred in 87% of patients, about 9 in 10
• Cytokine release syndrome (CRS, a systemic inflammatory response triggered by immune cells releasing large amounts of signaling proteins): occurred in 78% of patients, about 8 in 10
• Nonrash skin effects: occurred in 69% of patients, about 7 in 10

Grade 3 or 4 adverse events (severe or life-threatening) occurred in 76% of patients, about 3 in 4. The most common grade 3 or 4 events were cytopenias (low blood cell counts), including low red blood cells, white blood cells, or platelets. These were generally transient and resolved in most patients (87%).

Grade 3 or 4 infection occurred in 31% of patients — about 1 in 3 — which is a serious concern in this already immunocompromised population.

Treatment Modifications

Side effects frequently required adjusting treatment:

• Treatment modification due to adverse events: 62 patients (69%)
• Treatment modification due to infection: 27 patients (30%)
• Treatment cycles delayed due to adverse events: 55 patients (61%)

A nonfatal adverse event led to discontinuation of one or both drugs in 5 patients (6%):

• Both talquetamab and teclistamab were discontinued by 1 patient with grade 4 ICANS, 1 patient with dysphagia (trouble swallowing) and dry mouth, and 1 patient with pseudomonal pneumonia (a lung infection caused by Pseudomonas bacteria) and pseudomonal sepsis (a bloodstream infection)
• Talquetamab only was discontinued by 1 patient with dysgeusia (taste distortion) and dysphagia, and 1 patient with hypohidrosis (inability to sweat normally)

Of these 5 patients, 3 (3% of the total study population) had events deemed by the investigator to be related to the study treatment. Notably, no patients discontinued teclistamab only.

Deaths During the Study

Adverse events led to death in 10 patients (11%) during follow-up. Seven of those 10 patients had stable disease or disease progression at the time of death.

Five deaths were considered by investigators to be treatment-related:

• One death due to Covid-19–related pneumonia
• One due to Klebsiella pneumonia (a bacterial lung infection)
• One due to pneumonia from an unspecified infection
• One due to pseudomonal sepsis (a Pseudomonas bloodstream infection)
• One due to aspiration (inhaling food, liquid, or vomit into the lungs)

Five deaths were not considered treatment-related:

• One due to Klebsiella sepsis
• One due to cerebral hemorrhage (bleeding in the brain)
• One due to euthanasia
• One due to general deterioration of physical health
• One due to respiratory failure

Cytokine Release Syndrome Details

Cytokine release syndrome occurred in 70 patients (78%). All cases were grade 1 or 2 — meaning they were mild to moderate, not life-threatening. Most cases were confined to the step-up period and the first cycle of doses. Almost all CRS events (121 of an unspecified total) were managed with supportive care.

The authors note that the overall safety profile — including the high rate of grade 3 or above events — was consistent with what has been observed with each agent as a monotherapy in patients with relapsed or refractory myeloma.

What This Means for Patients

This study provides strong evidence that dual targeting of GPRC5D and BCMA with talquetamab plus teclistamab can produce meaningful responses in patients with true extramedullary myeloma — a group that has historically been extremely difficult to treat and has very poor outcomes with standard therapies.

The key takeaways for patients and families:

• Most patients respond: About 8 in 10 patients (79%) achieved at least a partial response, and about 5 in 10 (54%) achieved a complete response or better. For a disease where the expected response rate with standard treatments is dramatically lower (patients with true extramedullary disease being 87% less likely to respond than those without it), these numbers are notable.
• Responses can be durable: Nearly two-thirds of responders (64%) maintained their response for at least 12 months. The median duration of response was 13.8 months.
• It works after other modern treatments have failed: The 83% very good partial response or better rate in patients who had previously received anti-BCMA CAR-T therapy is particularly important. These patients had already been exposed to a BCMA-targeted therapy, and yet the BCMA-targeting teclistamab combined with the GPRC5D-targeting talquetamab still produced deep responses. This suggests that dual targeting can overcome resistance to single-antigen approaches.
• Monthly dosing is feasible: After the initial period, most patients (77% of responders) were able to switch to monthly dosing, and their responses did not suffer — 93% of responses deepened or were maintained after the switch.
• Side effects are significant but manageable: Most patients experienced oral symptoms, and about 8 in 10 experienced cytokine release syndrome, though CRS was always grade 1 or 2. Patients should expect that they may need dose adjustments or treatment delays (69% and 61% of patients, respectively), and they should be monitored closely for infections.

The authors note that the study's primary hypothesis — that the combination would achieve a response rate with a lower confidence bound exceeding 40% — was clearly met. The response rate of 79% with a lower bound of 69% is well above this threshold.

Limitations of the Study

Like all studies, RedirecTT-1 has limitations that patients and clinicians should understand when interpreting the results.

• No control group: This was a single-arm, nonrandomized study. There was no comparison group receiving standard therapy or either drug alone. While the results are strong, the lack of a control arm makes it harder to quantify the exact benefit compared with other treatment approaches.
• Modest sample size: With 90 patients, the study is relatively small, and subgroup analyses (such as the 8 patients with prior bispecific exposure) have wide confidence intervals that make precise estimates difficult.
• Confidence intervals not adjusted for multiplicity: The authors explicitly note that across primary and secondary end points, confidence intervals were not adjusted for multiplicity and should not be used to infer definitive treatment effects for the secondary outcomes.
• Follow-up duration: Median follow-up was 12.6 months. While the response duration and survival data are encouraging, longer-term outcomes — including how durable remission remains at 2, 3, or more years — are not yet known.
• Specific patient exclusions: Patients with only paramedullary disease, central nervous system involvement, or plasma-cell leukemia were excluded. Prior CAR-T patients were capped at 20% of the population, and patients who had previously received bispecific antibodies targeting GPRC5D or BCMA were excluded. Results may not be generalizable to these patient groups.
• A substantial portion of deaths were treatment-related: Five of 10 deaths (50%) were considered related to treatment, and 11% of the total study population died during follow-up. For a population with such advanced disease, separating treatment-related mortality from disease-related mortality is complex, but the risk is real.
• No quality-of-life measurement reported: The study did not report patient-reported quality-of-life outcomes, so the impact of the high side-effect burden on daily living is not fully captured in this publication.

Recommendations for Patients

For patients with relapsed or refractory multiple myeloma — especially those with true extramedullary disease — this study offers a meaningful new treatment consideration. However, treatment decisions must always be individualized, and here are key points to discuss with your oncology team:

1. Ask about bispecific antibody combinations: If you have true extramedullary disease and have exhausted or not yet tried bispecific antibody therapy, ask your doctor whether talquetamab plus teclistamab — or a clinical trial of a similar combination — might be appropriate for your situation.
2. Know your previous treatment history: The results suggest this combination works even in patients who have had prior CAR-T therapy. If you have received CAR-T or a bispecific antibody before, do not assume you are out of options.
3. Expect oral symptoms: Taste changes, dry mouth, and difficulty swallowing affected 87% of patients — nearly 9 in 10. Work with your care team in advance on a plan for managing these. Dietary modifications, artificial saliva, and other supportive measures can help.
4. Understand the infection risk: About 1 in 3 patients experienced a severe (grade 3 or 4) infection. Ask your doctor about preventive measures such as antibiotics, antivirals, or immunoglobulin replacement, and know what symptoms of infection to watch for.
5. Plan for the step-up period: Cytokine release syndrome most commonly occurs during the initial step-up dosing. During this period, patients are closely monitored so that CRS can be caught and treated early. This is a standard and manageable part of bispecific antibody treatment.
6. Ask about monthly dosing: If you respond well, you may be able to move to a monthly schedule after 4 to 6 cycles. In this study, 77% of responders made this switch, and responses were maintained or deepened in 93% of those patients — so the convenience of monthly visits does not appear to come at the cost of effectiveness.
7. Weigh the risks and benefits honestly: The response rate of about 8 in 10 comes with a real safety burden — 76% of patients experienced severe (grade 3 or 4) side effects, and the death rate during follow-up was 11%. Your oncology team can help you understand how these numbers apply to your specific case.

The study authors conclude: "Most patients with drug-resistant, true extramedullary myeloma had a response with talquetamab plus teclistamab. The incidence of adverse events of grade 3 or above was high and was consistent with previous observations for each agent as monotherapy."

Frequently Asked Questions

What are the common side effects?

Common side effects included oral symptoms like taste changes and dry mouth (87%), cytokine release syndrome (78%), and non-rash skin effects (69%). Severe (grade 3 or 4) side effects occurred in 76% of patients, most commonly low blood cell counts. Infections were also a concern, with 31% experiencing severe infections.

How long does treatment last?

Patients continued treatment until unacceptable side effects, disease progression, or other reasons. The median follow-up was 12.6 months. After 4 cycles with a very good partial response or better, or after 6 cycles regardless, patients could switch to monthly dosing. Most responders (77%) made this switch.

What should I discuss with my doctor about this treatment?

Ask if this combination is appropriate for your situation, especially if you have true extramedullary disease. Discuss management of oral symptoms, infection risk, and the step-up period for cytokine release syndrome. Also ask about the possibility of monthly dosing after initial cycles and weigh the benefits against the risk of severe side effects.

My extramedullary myeloma is resistant to treatment. Should I get a second opinion before trying talquetamab plus teclistamab?

A second opinion can help you decide whether talquetamab plus teclistamab is right for you. In a recent trial, 79% of patients with drug-resistant extramedullary myeloma responded, and 54% achieved a complete response or better. However, side effects were common, including oral symptoms, cytokine release syndrome, and infections. A second opinion can confirm your diagnosis, review your imaging and pathology, and discuss whether this dual-targeting approach is appropriate given your prior treatments. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab

Authors: S. Kumar, M.-V. Mateos, J.C. Ye, S. Atrash, H. Magen, H. Quach, M.P. Chu, S. Trudel, J. Richter, P. Rodríguez-Otero, H. Chuah, M. Gatt, E. Medvedova, S. Raza, D.H. Yoon, T. Ishida, J.V. Matous, L. Rosiñol, K. Onodera, E. Scott, C. Heuck, J. Zhang, T. Henninger, L. O'Rourke, P. Thakkar, M. Festa, L. Huang, J. Zhou, M. Takamoto, L. Pei, J. Lu, N. Au, M. Krevvata, S.Z. Usmani, and Y.C. Cohen, for the RedirecTT-1 Investigators Study Group

Publication details: The New England Journal of Medicine, 2026;394:51-61. Published December 7, 2025. DOI: 10.1056/NEJMoa2514752

Funding: Johnson & Johnson

Trial registration: RedirecTT-1, ClinicalTrials.gov number NCT04586426

This patient-friendly article is based on peer-reviewed research published in The New England Journal of Medicine. The original article was authored by the RedirecTT-1 study group, and the full text is available at NEJM.org.