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Original source: World Medical Innovation Forum
This video from World Medical Innovation Forum covered a lot of ground. Streamed.News selected 8 key moments and summarises them here. Everything below links directly to the timestamp in the original video.
Discover how a previously stagnant field of cancer treatment has been revolutionized by new drugs, and learn about the unique challenges faced by less common diseases in securing research funding.
AML Treatment Sees Major Advancements with 12 New Drug Approvals
Acute Myeloid Leukemia (AML) treatment has seen remarkable progress over the past 18 years, with 12 drug approvals including IDH and FLT3 inhibitors, and the transformative venetoclax and azacitidine combination therapy. This surge of innovation contrasts sharply with the decades of stagnation in AML treatment prior to 2010.
Despite these significant advancements, AML remains an uncommon disease, which unfortunately translates to less research funding compared to more prevalent cancers like breast, colon, or prostate cancer. This underfunding could hinder future drug development efforts, even as current therapies allow patients, such as a 90-year-old on venetoclax and azacitidine, to live years longer than previously possible.
"We've had 12 approvals in a period of, you know, I think six, seven years. I don't know, maybe it doesn't compare that favorably to other hemalignancies, but to us, this was a big deal."
Bristol Myers Data Influences FDA to Remove CAR-T REMS Requirements
Bristol Myers has highlighted that only two out of ten eligible patients currently receive cell therapy, largely due to logistical hurdles and reluctance from referring physicians. The company is committed to democratizing access to these therapies.
Data from their product, Breyanzi, demonstrated that acute adverse effects like CRS and ICANS typically develop within 15 days, influencing the FDA's decision to remove Risk Evaluation and Mitigation Strategy (REMS) requirements. This move is expected to streamline access and reduce barriers for patients needing CAR-T cell therapy.
"We're proud that a lot of the data came from Breyanzi... that certainly helped the FDA in their decision of removal of the REMS."
CAR-T Therapy Preferred for Multiple Myeloma Patients with Four Prior Lines
In multiple myeloma patients who have undergone four previous lines of therapy, CAR-T cell therapy is generally favored over bispecific antibodies due to its superior efficacy and durability. However, logistical factors, particularly the availability of a caregiver, can sometimes lead to the selection of bispecifics, which offer a more convenient patient experience.
While CAR-T therapies like ciltacabtagene autoleucel (cilta-cel) show promising long-term progression-free survival, there's a concern that prior use of BCMA-targeting bispecific antibodies could compromise the efficacy of subsequent BCMA-targeted CAR-T therapy. The evolving landscape of these treatments suggests that the gap in efficacy between CAR-T and newer bispecifics may narrow over time.
"All things being equal, we would tend to lean towards the CAR-T cell therapy before the bispecific antibody because... the CAR-T probably would have more juice and be a little bit more efficacious."
CAR-T Access Disparity: Over 90% at Specialized Centers vs. 11-20% Nationally
Specialized centers report that over 90% of eligible patients receive CD19 CAR-T cell therapy, a stark contrast to national claims data, which indicates only 11-20% of eligible patients access this treatment. This significant disparity is primarily attributed to logistical barriers rather than patient fitness.
Key obstacles include challenges with travel, lack of awareness among local oncologists, and the necessity for a caregiver during the treatment process. These findings underscore the need to address systemic and practical issues to broaden access to advanced cancer therapies.
"At our center specifically, it's probably... over 90% of patients who actually get a CAR once they're consulting with us. That's in stark contrast to claims data for all eligible patients which ranges from 11 to 20%."
CAR-T Preferred First-Line for Lymphoma Due to Durability Data
For lymphoma, CAR-T cell therapy is generally preferred as a first-line treatment due to its five-year durability data, which shows approximately 40% of patients remaining disease-free and alive. Bispecific antibodies, specifically CD3/CD20 agents, are typically reserved for patients with logistical challenges or fitness concerns, as their durability data as single agents is more modest.
When choosing among bispecific products, patient logistics often dictate the decision, such as the route and frequency of administration. For instance, some patients might prefer a less frequent intravenous infusion over weekly subcutaneous injections, depending on their geographic location and commuting capabilities.
"I still start with CAR-T cells in all patients unless they really are not able to get a CAR-T cell because of a logistical or fitness reason. My rationale for that is that we have five-year durability data on CAR."
CAR-T Therapy Requires Robust Hospital Infrastructure Despite Safer Products
Even with increasingly safer CAR-T cell therapy products, community hospitals require robust infrastructure to manage rare but severe toxicities. This includes access to Intensive Care Units (ICUs) and specialized neurology or pulmonary critical care programs.
Hospitals must either achieve sufficient patient volume to justify the significant investment in specialized training and facilities, or the products must become so safe that severe events are rare enough to allow easy referral to larger, high-level centers. This underscores the economic and resource challenges in expanding CAR-T access beyond major academic institutions.
"You still have to have the infrastructure in place to handle that, especially if your volume is such that you're only going to treat, you know, 15 patients a year."
CAR-T Treatment Selection Balances Efficacy, Toxicity, and Logistics for Lymphoma
The selection between CAR-T therapies like Yescarta (axicel) and Breyanzi (lisacel) for large B-cell lymphoma involves a complex balance of clinical data, efficacy, toxicity profiles, and logistical considerations. While Yescarta demonstrated a survival benefit, trial design differences mean efficacy is often considered comparable between the two, despite varying national opinions.
Key factors influencing selection include the specific disease indication, turnaround times for product availability, and the patient's overall fitness to handle potential toxicities. Clinicians integrate projected arrival dates of cell therapy products with individual patient characteristics to make the most appropriate choice.
"I generally consider the efficacy data to be comparable though there are differences of opinion in terms of that nationally. The toxicity profile is more favorable with lisacel however the availability in terms of how long it takes to get the product from collection is on average about 5 to 7 days longer for us."
Sequencing CAR-T First Optimizes Efficacy, Anticipating Future Complexities
Sequencing CAR-T cell therapy before bispecific antibodies can optimize efficacy by preserving T-cell fitness, as constant antigen stimulation from bispecifics can impair endogenous T-cells. Retrospective data supports this approach, maintaining better outcomes for patients.
The treatment landscape is expected to become more complex as bispecifics gain approval for earlier lines of therapy. This will necessitate more nuanced clinical decisions, especially concerning the potential impact of prior bispecific use on subsequent CAR-T efficacy, highlighting the need for careful strategic planning in cancer treatment.
"Giving a CAR-T first, you maintain the efficacy and it's optimized versus when you give it after a bispecific therapy."
Summarised from World Medical Innovation Forum · 44:45. All credit belongs to the original creators. World Medical Innovatio Forum summarises publicly available video content.
