High-potency chemo may hurt, not help in myeloma treatment
Researchers find bridging therapy can add toxicity without benefits
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A new study by U.S. researchers suggests that using high-potency chemotherapy in myeloma as part of bridging therapy — medications given before patients are administered the cell therapy Carvykti (ciltacabtagene autoleucel) — may actually increase the risk of safety complications without meaningfully improving the odds of successful treatment outcomes in some cases.
The scientists noted that, while targeted treatments can successfully reduce a person’s tumor burden prior to Carvykti’s use, these new data indicate that certain meds used during bridging therapy may negatively influence outcomes with the infusion therapy, used for hard-to-treat myeloma. The team found that high-potency chemo during bridging therapy — used in the period between when patients start the process of getting treatment and when it’s administered — can potentially lead to worsened disease for some patients.
Importantly, however, the data showed that more than half of patients given this bridging therapy experienced a reduction in disease activity when it was used before Carvykti. The researchers stressed that their findings “[underscore the need for] a patient-specific approach, where treatment is tailored based on [the individual] … rather than adhering to a uniform treatment strategy.”
According to the team, “our findings support optimizing [bridging therapy] beyond disease control, with the goal of achieving biochemical evidence of decreased disease to enhance the benefit-risk profile of [Carvykti].”
The study, “Bridging therapy response and type as determinants of cilta-cel outcomes in relapsed/refractory multiple myeloma,” was published in Blood Cancer Journal. The work was funded in part by Legend Biotech and Johnson & Johnson, the companies that developed Carvykti. Among the study’s more than 30 authors, five are employed by Johnson & Johnson, and one by Legend. The work was led by scientists at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida.
Myeloma is a type of blood cancer marked by the uncontrolled growth of plasma cells, a type of immune cell. Carvykti, approved in the U.S. and Europe since 2022, is used to treat certain adults with myeloma that is relapsed or refractory, meaning the cancer came back or failed to respond after prior treatments.
High-potency chemo often given prior to Carvykti in myeloma
Carvykti is an autologous CAR T-cell therapy. This type of treatment involves collecting T-cells, a type of cancer-killing immune cell, from a patient. The cells are then taken to a lab to be equipped with a chimeric antigen receptor (CAR), a human-made protein that directs them to attack a specific target. With Carvykti, the CAR specifically targets a protein called BCMA, which is expressed by plasma cells.
Once the cancer-killing immune cells are prepared, patients undergo a round of chemotherapy to eliminate existing immune cells, and then the therapeutic cells are administered. But it takes a few weeks from the time a patient’s T-cells are collected to when the individual starts Carvykti treatment. In that time, patients are often given additional anticancer treatments known as bridging therapy.
Various myeloma treatments may be used as part of bridging therapy. However, even though this type of treatment is common, minimal data exist on whether or not different types of bridging therapies affect the outcomes of Carvykti treatment.
To learn more, the research team analyzed outcomes from nearly 200 patients undergoing Carvykti treatment in real-world settings.
“Despite the potential to optimize safety and efficacy post-CAR-T, evidence linking specific [bridging therapy] strategies and [bridging therapy] response to [Carvykti] outcomes remains limited, the researchers wrote. “Therefore, this study aimed to characterize [bridging therapy] use and clinical outcomes by [bridging therapy] regimen among patients with [relapsed/refractory myeloma] treated with [Carvykti given according to standard commercial guidelines].”
The team added that, “to our knowledge, this study represents the first large real-world evaluation of [bridging therapy] prior to [Carvykti], providing important insights outside the context of a clinical trial and contributing meaningful data on outcomes in a broader patient population.”
Over 45% of patients had stable or worse disease after meds
Among the total 192 patients who received Carvykti, 90% underwent some type of bridging therapy, the data showed. Specific medications used as part of bridging therapy comprised chemotherapies, immunomodulatory agents, proteasome inhibitors, and the therapy Talvey (talquetamab).
The researchers noted that exact regimens varied substantially, reflecting that this type of treatment is usually “tailored based on disease characteristics, prior treatment exposure, baseline clinical risk factors, and anticipated tolerability,” and not given by any strict standard treatment strategy.
Among patients with available data, slightly more than half (54%) experienced a reduction in disease activity after bridging therapy and before Carvykti administration. The remaining 46% had stable or worsened disease after bridging therapy, the team noted. Reductions in disease activity were most common among those given Talvey or proteasome inhibitors as part of bridging therapy.
“More than half of the patients achieved biochemical evidence of decreased disease during [bridging therapy], although response rates differed markedly by regimen type,” the researchers wrote.
Patients with decreased disease after bridging therapy generally had fewer risk characteristics, such as lower rates of high-risk genetic mutations in their cancer cells. These individuals also generally had better outcomes, including lower rates of serious safety complications and a lower risk of death or disease progression over the course of follow-up.
Further studies are warranted to … define optimal [bridging therapy] strategies. … These emerging data … [support] a shift away from intensive [cell-killing] chemotherapy when feasible.
The researchers noted that it’s difficult to tease out cause-and-effect in these relationships. Still, the data suggest that responses to bridging therapy may help predict long-term outcomes with Carvykti, the team noted.
Additional research is needed to explore this possibility further, the scientists said, writing that “further studies are warranted to validate these findings and define optimal [bridging therapy] strategies.”
The researchers also highlighted that patients given bridging therapy using chemotherapies were significantly more likely than those given other regimens to experience severe low blood cell counts, without any indication that disease outcomes were better.
“These emerging data suggest that less intensive, immune-directed BT may better balance disease control with preservation of [blood cell counts] and post CAR-T outcomes, supporting a shift away from intensive [cell-killing] chemotherapy when feasible,” the researchers wrote.
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