Quest persists for ideal Covid-19 booster timelines in blood cancers
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Quest persists for ideal Covid-19 booster timelines, vaccine mixing in blood cancers

By Manasi Vaidya 14 Oct 2021 (Last Updated October 14th, 2021 17:26)

While the FDA contemplates Covid-19 booster use, researchers have begun investigating their activity in blood cancer patients.

Quest persists for ideal Covid-19 booster timelines, vaccine mixing in blood cancers
Experts are exploring ideal booster timing for Covid-19 vaccines for patients with blood cancers. Image Credit: Shutterstock

Need to know:

  • Covid-19 vaccine booster timing could be patient-specific considering ongoing cancer treatments.
  • There is interest in Moderna’s Spikevax as a booster regardless of a patient’s initial vaccine.

As Covid-19 vaccine booster data in cancer patients start to accumulate, experts continue to explore ideal booster timelines, such as in cases that involve B-cell-suppressive treatments for haematological cancers. Also, the potential to use heterologous boosters has piqued interest among physicians.

On 12 August, the FDA authorized a booster dose of Pfizer and BioNTech’s Comirnaty (BNT162b2) and Moderna’s Spikevax (mRNA-1273) in immunocompromised individuals, as well as expanded Comirnaty’s booster authorization to include certain at-risk populations. In the next couple of days (14 and 15 October), the FDA is holding a Vaccines and Related Biological Products Advisory Committee (VRBAC) meeting to discuss the use of Spikevax and Johnson & Johnson’s (J&J) respective Covid-19 vaccines as boosters for individuals older than 18 years old.

The US Centers for Disease Control and Prevention (CDC) recommends getting a third dose after six months. However, as more cancer patients receive these boosters, the ideal gap between the second dose and the booster in immunocompromised people is still being actively investigated. This question is particularly pertinent since some received the third dose sooner than other patients, and may receive treatments capable of suppressing the potential for an effective vaccine-induced immune response.

The ideal gap between the second dose and the booster in immunocompromised people is still being actively investigated.

Currently, the CDC recommends a third dose of the same mRNA vaccine as the first two doses. However, early encouraging efficacy with Spikevax as a booster and the potential to use a different vaccine approach than the primary vaccine has opened the possibility of improving the immune response. The potential use of heterologous or ‘mix and match’ boosters will also be discussed at the ongoing VRBAC meeting.

There is no guidance on using the authorized J&J’s Ad26.Cov2.S, an adenovirus-vectored vaccine, as a booster for immunocompromised individuals. There are relatively few cancer patients who received the single-dose J&J vaccine as a primary vaccine, but a guidance on the ideal booster for these patients is still urgently needed. The company is planning regulatory submissions based on recent data showing it causing a 12-fold increase in antibodies at six months.

Waning antibody levels argue for booster

The working assumption for boosters is that patients with low, undetectable, or waning antibody levels should get it, said Leukemia and Lymphoma Society (LLS) chief scientific officer Dr Lee Greenberger. The messaging is particularly clear for their use in immunocompromised patients, said National Cancer Institute breast cancer and melanoma therapeutics head Dr Larissa Korde. Since the immune system is not as robust in cancer patients, a booster is crucial for improved immune response, she added.

Based on data with 49 haematological cancer patients from the Leukemia & Lymphoma Society National Registry, 35% were seronegative after an initial vaccination or booster. But the rest had an increase in antibody levels such that they were seroconverted or seroelevated after the booster.

Once the concept of a booster reached mainstream discussion, a number of patients with haematological cancers got a third shot even before the CDC came out with an official guidance, experts said. This has allowed for several groups to follow these patients and collect serological and safety data on their immune response.

The ideal timing can get tricky as guidelines have been indicated for people on active therapy.

In general, the CDC recommends a booster to be given six months after the second vaccine dose, but this does not include any distinct message for immunosuppressed individuals. The ideal timing can get tricky as guidelines have been indicated for people on active therapy, but they failed to capture the people who have had therapy within six months or one year, said Lifespan Cancer Institute haematologist oncologist Dr Thomas Ollila in Rhode Island.

A booster is strongly recommended for elderly and immune suppressed cancer patients who had their second vaccine dose several months ago. But this guidance may be different for someone who received the last dose less than four months ago, said Montefiore Health Systems oncology program director Dr Balazs Halmos.

When it comes to identifying the right gap between the final vaccine dose and booster, if lymphopenia is expected to resolve and B cell counts are expected to continue to recover after cancer treatment, then it makes sense to wait on a booster. Also, that recovery period can vary. In haematological cancer patients who do not mount any immune response to the vaccine, booster timing may be up to the physician, pending on the disease and ongoing treatment, Greenberger and Ollila said.

Ideal vaccination timing complex

The ideal timing for vaccination or a booster with regard to Roche and Biogen’s anti-CD20 antibody Rituxan (rituximab) treatment is complex. Rixtuan’s immunosuppressive effect could take 9–12 months to wear off after treatment. Nonetheless, the Leukemia & Lymphoma Society (LSS) is advocating to not hold up treatments while making vaccination or booster decisions, Greenberger said.

Even suspending Bruton tyrosine kinase (BTK) inhibitors, which impact B cell function, to consider vaccination response needs to be done carefully with physician guidance because this action can cause a rapid disease advancement in chronic lymphocytic leukemia (CLL) or mantel cell lymphoma, Greenberger said. BTK inhibitors like Imbruvica (ibrutinib), manufactured by Janssen Pharmaceutical companies of J&J and Pharmacyclics, an AbbVie company, are approved to treat CLL and other haematological cancers. However, BTK inhibitor treatment is not a consistent negative indicator of vaccine response, and some can respond after a booster, Greenberger said.

Upcoming data that can provide granularity on the ideal timing of doses in immunosuppressed patients is missing, said Korde, who is involved with a longitudinal National Cancer Institute study to track serological changes to characterize the immune response in cancer patients. More data is expected, especially from places with an early widescale deployment of boosters like in Israel, said Sheba Institute of Oncology senior oncologist Dr Ido Wolf. Boosters were recommended for those with a weakened immune system on 11 July in Israel.

Even in the case of solid tumors, if patients on chemotherapy or immunotherapy respond well to the vaccine, there is no reason to modify those schedules, Halmos said. Theoretically, giving boosters before starting chemotherapy makes sense, but there is no data to guide decisions based on that rationale, said Wolf. Nonetheless, there been no unusual safety responses to the boosters, similar to the primary vaccination for such individuals, Greenberger said.

Booster switch potential draws curiosity

One of the next questions is to explore whether a different type of shot used as a booster compared to the primary vaccine can elicit a better immune response. An imminent trial, with National Cancer Institute’s (NCI’s) support, will explore the potential of whether switching vaccines for the booster shot can improve the immune response, Halmos said. Greenberger added imminent data on heterologous vaccine-booster strategies could be conceivable from the LLS registry.

Data on heterologous booster use that is not limited to only cancer patients will be released at the ongoing FDA’s VRBAC meeting on boosters.

LLS data indicate that Spikevax generates a higher seroconversion rate compared to Comirnaty. Even Ollila’s group found that in using anti-Spike antibodies as a surrogate, Spikevax led to the best serconversion, followed by Comirnaty and the J&J vaccine. Based on this, it would be great to have guidance or authorization to give Spikevax as a booster regardless of the primary vaccine, Ollila said.

The right dose to induce immunity remains unknown; even Moderna is now considering a booster with a lower dose.

However, one remaining caveat to making a direct comparison between the two mRNA vaccines is that they use different doses, and whether that impacts the efficacy is less understood, Greenberger said. The right dose to induce immunity remains unknown; even Moderna is now considering a booster with a lower dose, he added. Also, it remains to be seen if one booster is enough for protection or if two are required, Ollila said.

Nonetheless, there is not yet enough data to inform whether switching to a different vaccine for a booster will change the immune response, Korde said. The underlying reason why patients cannot mount an immune response is more likely because their immune system is weak, not because of the vaccine, she added.