All immunity: an opinionated take on NEJM highlights for February 2021

We can cure Hep C but not immunize against it

Sovaldi and other drugs have made curing chronic Hepatitis C a routine, if expensive, proposition. Still, given how common Hep C infection is, and how it can irreversibly damage the liver without overt signs, a vaccine would be highly valuable. Unfortunately, an NIH sponsored trial with a GSK vaccine in 548 IV drug users at high risk of contracting the disease failed to show any protection: 28 participants developed chronic Hep C evenly divided between the placebo and treatment groups.  Given that persons who are cured from Hep C with antivirals are susceptible to reinfection, I don’t think that the probability of a successful vaccination strategy is high. Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection


Passive immunity for Covid-19 works, sometimes

The use of plasma from patients who have recovered from an infection is an old concept, but one that tends not be used much anymore.  While we wait for broad access to Covid-19 vaccines, there have been renewed attempts to use this strategy – after all, since the vast majority of individuals have mild disease, it is possible to harvest substantial convalescent plasma.  A couple randomized placebo controlled trials from Argentina have tested how effective this strategy might be.  They found that plasma administered early (within 72 hours of onset of symptoms and before they are severe) results in a 50% reduction in patients progressing to severe disease (and 70% when using plasma with high antibody concentration). On the other hand, later use when severe symptoms are present does not appear to have a clinical benefit. In some ways this replicates the experience with special purpose antibodies for Lilly and Regeneron, but with the advantage that this is accessible to any country with a working blood banking system. Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults; A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia (free access)


Induced immunity for Covid-19: Israel’s experience

Whenever an intervention is rolled out over time, there is an opportunity to study the effect by a contemporaneously synchronized comparison of the sample that has already received the intervention vs. the sample that has not yet received it. It does not eliminate the potential for selection bias but has the advantage of providing evidence in a setting that is more similar to Real World than within an RCT. It’s rare to see these methods used in the setting of clinical interventions and that’s what makes this large study about mass vaccination in Israel fascinating.  In the course of the deployment of the BioNTech/Pfizer vaccine, a large integrated health organization systematically attempted to match any person getting vaccinated to a control person with similar demographic characteristics who had not yet been vaccinated. This resulted in 596,618 matched pairs who were discordant for vaccination status for a duration ranging from 1 to 42 days (i.e. whenever the control got vaccinated).  Findings were consistent with registration trial findings (e.g. 94% protection from symptomatic disease 7 days after the 2nd dose).  But this is a methodology that could be used more systematically in the introduction of new therapies.  BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting


Cell based immunity for blood cancers – maturing fast

A letter to the editor describing the long-term follow-up of patients with refractory B-lymphoma treated with tisagenlecleucel (Kymriah, Novartis) as previously described in this blog 4 years ago showing that most patients who achieve remission at 1 year are progression free at 5 years. No doubt that those kind of results in patients who were at death’s door having exhausted many other therapies will support some discussions with payers on the price tag.  Five-Year Outcomes for Refractory B-Cell Lymphomas with CAR T-Cell Therapy

Meanwhile a phase 2 in multiple myeloma for another CAR-T, idecabtagene vicleucel (ide-cel, also called bb2121, bluebird/BMS) following a phase 1 described in this blog 2 years ago. This was a single group trial (though with multiple doses) in patients with advanced disease (median 6 prior therapies).  At a high dose, 81% had a response, but unfortunately these are typically not sustained much beyond 12 months (although the follow-up is insufficient to judge whether some patients will benefit from a long term remission). It’s very likely enough for an approval (PDUFA date March 27 2021) – but the real potential in my view is for earlier use which might result in cures.  This trial is on-going. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma


The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.