Need to know:
- B-cell directed therapies make vaccine efficacy variable depending on cancer subtype
- Solid tumour patients show encouraging seroconversion rates despite chemo and immunotherapy
- Upcoming research will shed more light on boosters and nuances in immune responses
Emerging data indicates available Covid-19 vaccines do not offer the same level of protective immune response in all haematological cancers as they do in solid tumours, prompting some caution. And so, masks and other Covid-19 protective measures continue to remain necessary for patients particularly with blood cancers, experts said.
The nature of haematological cancers and immunosuppressive regimens impede adequate Covid-19 vaccine response in certain subtypes according to emerging data. Moreover, anti-CD20 antibodies like Roche/Biogen’s Rituxan (rituximab) or BTK inhibitors like Imbruvica (ibrutinib), manufactured by Janssen and Pharmacyclics, an AbbVie affiliate, particularly reduce the chances of a patient from seroconversion. This is true especially during treatment, but the immunosuppressive effect has been seen even months after therapy is done.
In contrast, studies tracking Covid-19 vaccine efficacy in solid tumour patients have shown that a larger proportion of patients seroconvert and have protective antibodies following vaccination.
When it comes to estimating vaccine-induced protection, there is a tendency to measure anti-spike antibodies while considering vaccination or a booster. But experts shied away from relying on them completely to assess the level of protection a particular patient may have against the virus and said it was still an evolving science.
Both the EMA and FDA recommend boosters for people with weakened immune systems. As more patients get these boosters, experts expect studies to shed light on factors that could influence serological changes after vaccination.
Protective measures crucial despite vaccines
Being hit early and hard by the pandemic in New York, Montefiore Health Systems oncology program director Dr Balazs Halmos said it was clear that Covid-19 could be a serious illness for cancer patients associated with age, frailty, and comorbidities. Those with haematological malignancies tend to be immunosuppressed, so these patients among those with the highest mortality, he added.
Prior to the spread of the SARS-CoV-2 Delta variant, Lifespan Cancer Institute haematologist oncologist Dr Thomas Ollila in Rhode Island, said he was comfortable saying that cancer patients could have small family gatherings with vaccinated people. Now, however, that may not be the case. Full vaccination still offers imperfect immunity, so cancer patients need to remain vigilant about distancing and masking and limiting their indoor contact, added National Cancer Institute breast cancer and melanoma therapeutics head Dr Larissa Korde.
Recent cohort studies have indicated that while those with solid tumours are generally able to mount an immune response after getting a Covid-19, a relatively larger proportion of haematological cancer patients are not able to do so.
For example, in an Israeli retrospective study of 326 solid tumour patients who got Pfizer/BioNTech’s Comirnaty (BNT162b2), only 11.9% were seronegative compared to 5% in a control group. However, in a serological analysis done in 1,375 patients with different haematological malignancies after Comirnaty or Moderna’s Spikevax (mRNA-1273), about a quarter did not seroconvert. Seronegative rates depend on the cancer subtype, ranging from 42–75% in non-Hodgkin’s lymphoma, one of the more common blood cancers.
In the Israeli study, when ongoing treatments are considered, seronegativity was higher in the chemotherapy-treated group (18.8%) compared to the checkpoint inhibitor-treated patients (9.1%) and those on targeted therapy (2.6%). However, even if these patients developed a lower level of protective antibodies than those without cancer, the titers were still considered protective, said Sheba Institute of Oncology senior oncologist Dr Ido Wolf.
Treatments for haematological malignancies are directed against cellular immunity while it’s driven toward the tumour in the case of solid cancers, Wolf explained. For patients with haematological malignancies, especially those who received immunosuppressive treatments like CAR-T, stem cell therapies or anti-CD20 antibodies, they have lower seroconversion. Even 6–12 months after Rituxan treatment, its suppressive effects remained, said Leukemia and Lymphoma Society (LLS) chief scientific officer Dr Lee Greenberger. This could indicate that if a patient is over a year from treatment, there may be a rapid response after vaccination, but not before that, Ollila added. Nonetheless, the LLS Society is advocating to not hold up treatments while making vaccination or booster decisions, Greenberger said.
Serological analysis to provide greater insight
In terms of gauging the immune response to determine vaccine schedules or boosters, Ollila mentioned the use of antibody tests to help guide patients. However, Wolf recommended against relying on antibody tests alone because the levels required for protection are still unknown. Even those with high antibodies should continue to mask in public and have household members vaccinated, Wolf said. Serological analysis to measure antibodies is an imperfect science and there is no gradient cutoff to say if a patient is fully protected or not, Korde said. Also, only a fraction of the anti-spike antibodies are neutralizing antibodies, Greenberger said.
Nonetheless, Wolf emphasized that despite any remaining questions on protective efficacy, the vaccines have not shown any major safety issues in cancer patients. This is especially significant given the fact that COVID-19 can be a serious illness for those with a cancer diagnosis.
Whether people with haematological cancers are a higher risk of breakthrough infections or symptomatic disease leading to hospitalisation and death remains to be studied, Greenberger said. A large analysis of T cell and B cell response levels is needed to understand the cutoff and timeline for protection, he said. The latter question will be necessary to decide whether patients will require a second booster. Halmos is leading a Phase II trial studying the immune response generated after boosters in cancer patients on the role of humoral or B-cell immunity and cellular or T-cell immunity. The trial will show how patients may respond to boosters based on the seroconversion rate, he added.