Real-world patient profile and step-up dosing process of early initiators of teclistamab for multiple myeloma in US hospitals An analysis using the Premier Healthcare Database

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PACUPod is your trusted source for evidence-based insights tailored to advanced clinical pharmacists and physicians. Each episode dives into the latest primary literature, covering medication-focused studies across oncology, and many more. We break down study designs, highlight key findings, and objectively discuss clinical implications—without the hype—so you stay informed and ready to apply new evidence in practice. Whether you’re preparing for board certification or striving for excellence in patient care, PACUPod helps you make sense of the data, one study at a time.

Britany: Welcome back to PACULit, your go-to podcast for the latest clinical literature updates. Today, we’re diving into a real-world study on teclistamab, a bispecific antibody for relapsed or refractory multiple myeloma. Seth, have you been following recent data on teclistamab outside clinical trials?

Seth: Absolutely, Britany. The accelerated approval of teclistamab was a game-changer after the MajesTEC-1 trial showed promising efficacy with manageable safety, especially regarding cytokine release syndrome or CRS. But until now, we lacked a comprehensive look at how this therapy performs in real-world hospital settings, including patient profiles and the step-up dosing process.

Britany: Exactly. Tan and colleagues addressed this in a retrospective observational study using the Premier Healthcare Database. They analyzed 413 adults with multiple myeloma who started teclistamab between November 2022 and September 2023 in US acute care hospitals. This fills gaps since MM patients are often older with multiple comorbidities, and real-world data on dosing logistics and CRS management have been sparse.

Seth: That’s key. Multiple myeloma remains incurable with frequent relapses despite advances. Bispecific antibodies like teclistamab target BCMA, a promising antigen on malignant plasma cells. CRS is a significant immune-mediated toxicity requiring careful monitoring. Understanding step-up dosing outside trials is vital for pharmacists and physicians managing these complex patients.

Britany: The study’s focus on real-world demographics is insightful. Median age was 69, nearly half over 70. The cohort was racially diverse—about 63% White and 24% Black—and predominantly male. Most patients were treated in large urban teaching hospitals, reflecting where complex MM care is concentrated.

Seth: The comorbidity burden was substantial. Nearly half had anemia, 40% peripheral neuropathy, and over a third renal impairment or failure. These complicate treatment and highlight the importance of real-world safety data. The study also examined step-up dosing completion and logistics, crucial since the label recommends specific dosing escalation to mitigate CRS risk.

Britany: Regarding step-up dosing, among 302 patients who completed it, over 91% did so within a single inpatient admission, averaging 8.7 days. That’s a significant inpatient commitment but aligns with the need for close monitoring during initial dosing.

Seth: Yes, dosing intervals between step-up doses were mostly two or three days apart, matching the FDA-approved regimen. This real-world adherence reassures that hospitals implement label recommendations effectively.

Britany: On CRS incidence, about 32% experienced CRS based on ICD-10 coding, mostly grade 1 or 2, with only 1% grade 3. The Keating algorithm, supplementing claims data by identifying CRS symptoms, showed a similar 28.5%. Fever and hypotension were the most common CRS symptoms.

Seth: That’s notably lower than the 72% CRS incidence in MajesTEC-1 but consistent with other real-world studies like Xie et al., reporting 54%. Variations likely reflect differences in populations, monitoring, and coding. Importantly, most CRS events were mild and manageable.

Britany: Management was well documented. Nearly all patients with CRS received dexamethasone and acetaminophen; diphenhydramine was used in over three-quarters. Tocilizumab, the IL-6 receptor antagonist, was given in about 30%, highlighting its role in mitigating more severe CRS.

Seth: This aligns with Singh et al.’s findings emphasizing proactive CRS management, including tocilizumab to reduce severity. A clinical pearl for pharmacists: early recognition and intervention prevent treatment interruptions and improve outcomes.

Britany: Despite high comorbidity, most patients completed step-up dosing without severe CRS complications, supporting teclistamab’s feasibility in a diverse real-world population often underrepresented in trials.

Seth: The study’s strengths include its large, diverse cohort and detailed analysis of dosing logistics and CRS management. Limitations include its retrospective design and reliance on claims data, which may underreport CRS severity and symptoms.

Britany: Also, it didn’t capture outpatient-only patients, so findings mainly reflect inpatient initiation. European expert guidelines and some US studies suggest outpatient step-up dosing might be feasible for selected patients, potentially reducing hospital stays.

Seth: That’s promising. Kowalski et al. showed prophylactic tocilizumab could reduce CRS incidence, facilitating safer outpatient dosing. Integrating such strategies could optimize resources while maintaining safety.

Britany: On pharmacokinetics, Guo et al.’s modeling based on MajesTEC-1 supports the current dosing regimen’s rationale, balancing efficacy and toxicity. This mechanistic insight reinforces the clinical dosing schedule.

Seth: Comparing teclistamab to other BCMA-targeting bispecifics, Lee et al.’s indirect comparison suggests comparable efficacy and safety, though direct head-to-head trials are needed.

Britany: So, Seth, clinical implications for pharmacists and physicians managing MM patients starting teclistamab?

Seth: First, expect an older, comorbid population needing careful assessment. Second, anticipate an inpatient step-up dosing process averaging nine days with close monitoring for CRS symptoms like fever and hypotension. Third, be ready to manage CRS proactively with dexamethasone, acetaminophen, diphenhydramine, and tocilizumab as needed. Finally, consider emerging evidence supporting outpatient dosing and prophylactic strategies to improve convenience and reduce hospital burden.

Britany: Good points. Given common comorbidities like renal impairment and neuropathy, pharmacists should review concomitant meds carefully to avoid interactions that could worsen toxicity or affect teclistamab metabolism.

Seth: Definitely. While teclistamab is a monoclonal antibody with limited CYP metabolism, supportive drugs like dexamethasone can induce CYP enzymes, potentially affecting other meds. Vigilance is key.

Britany: Before we wrap up, further prospective studies are needed to validate outpatient step-up dosing, prophylactic CRS mitigation, and long-term safety and efficacy in real-world populations.

Seth: Agreed. Tan et al.’s study provides a solid foundation, but ongoing research will refine teclistamab’s role and optimize patient management.

Britany: To summarize, this real-world analysis confirms teclistamab initiation in US hospitals involves older, racially diverse patients with significant comorbidities, yet most complete label-recommended step-up dosing safely. CRS incidence is manageable with established interventions, supporting teclistamab’s expanding use outside trials.

Seth: Absolutely, Britany. This study offers practical insights into dosing logistics and safety, enhancing confidence in using teclistamab for relapsed/refractory multiple myeloma.

Britany: Thanks for joining me today, Seth. And thank you to our listeners for tuning into PACULit. Stay tuned for more clinical literature updates.

Seth: Thanks, Britany. Looking forward to our next deep dive. Until then, keep advancing patient care with evidence-based practice.

Britany: Take care, everyone!