At ASH 2025, the presentation that stuck with me wasn't another incremental BCMA readout. It was a four-patient dataset on in vivo CAR T u2014 a viral particle approach that reprograms T cells inside the body without any apheresis, bridging therapy, or ex vivo manufacturing. Four patients. All achieved MRD negativity at 10u207bu2075. Involved free light chains went to zero. M spikes dropped. Soluble BCMA followed.
Four patients is not a signal. But the architecture is. If you can inject viral particles with T-cell tropism, wait two weeks for CAR T cells to emerge endogenously, and skip the entire apheresis-to-infusion logistics chain u2014 that's not an incremental improvement. That's a category change. The current CAR T bottleneck in myeloma isn't efficacy, it's throughput. Manufacturing slots, bridging decisions, lymphodepletion scheduling, CRS management inpatient. In vivo CAR T doesn't make those problems smaller u2014 it makes them irrelevant.
The rest of ASH filled in context around the sequencing problem that in vivo CAR T would eventually dissolve. CARTITUDE-1 five-year data showed roughly a third of patients in ongoing remission u2014 a number people are starting to use the word "cure" around, carefully. That's meaningful, but it also sharpens the question of who gets CAR T when, and what you've already exposed them to. The myeloma CAR T consortium data was unambiguous: prior BCMA exposure tanks outcomes. PFS drops. OS drops. The CAR T2-2 cohort C data showed it directly u2014 patients with prior BCMA therapy had substantially lower ORR and shorter duration of response than BCMA-naive patients in an otherwise similar population.
This is where the BCMA versus GPRC5D sequencing question becomes commercially loaded. Teclistamab targets BCMA. Talquetamab targets GPRC5D. If you use a BCMA bispecific as bridging before BCMA-targeted CAR T, you are potentially burning your best downstream option. The Cedars-Sinai bridging data showed bispecifics outperforming chemo and CD38/SLAMF7 antibodies for debulking u2014 100% response rate in a small series versus 50% for chemo. But that benefit calculation changes entirely if the bispecific you're choosing forecloses on CAR T efficacy later.
The commercial implication is that pharma teams selling into this space are now selling into a sequencing conversation, not a single-line decision. GPRC5D-targeted agents gain value specifically because they don't consume the BCMA pathway. Telcatamab plus teclistamab combination data from Redirect One showed 80-90% ORR, with particular strength in extra-medullary disease u2014 historically one of the hardest subgroups. That combination is expensive, complex, and comes with infection and skin toxicity burden. But for high-risk patients who've exhausted BCMA options, it's a serious option.
What pharma commercial teams should actually be watching: the tocilizumab prophylaxis story. CRS rate went from roughly 80% to 20% with prophylactic tocilizumab in CAR T patients. That's not a safety footnote u2014 it's an access driver. Outpatient CAR T administration becomes a real conversation when you can get CRS under control proactively. The centers that build outpatient CAR T protocols first will pull referrals from community oncologists who can't manage inpatient CRS. That's a KOL positioning story and a reimbursement story simultaneously.
The five-year CARTITUDE-1 data and the in vivo CAR T first-in-man results are telling the same story from different directions: myeloma is becoming a disease where durable remission is achievable for a meaningful subset of patients, and the question is how to engineer the treatment sequence to maximize who gets there. The commercial teams that understand the sequencing logic u2014 not just their own drug's label u2014 will be the ones writing the field's playbooks over the next three years.