The Leukemia & Lymphoma Society’s National Patient Registry COVID-19 vaccination antibody results - published today (Greenberg et al)

[lankisterguy]

As a valued member of The Leukemia & Lymphoma Society’s National Patient Registry, a project of the Michael J. Garil Patient Data Collective, we wanted you to be among the first to know about COVID-19 vaccination antibody results we published today (Greenberg et al., 2021).

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Thanks to the commitment of the more than 8,000 blood cancer patients and survivors who joined the Registry, LLS has published the largest and most comprehensive study to date to help patients and their healthcare providers make more informed decisions about how to remain safe during the ongoing pandemic.

This study is based on data from 1,445 of the 8,000 Registry participants who had antibody blood tests between March 12 and May 5, 2021. A sensitive blood test was used to measure antibody levels in patients at least two weeks after their second dose of either of the mRNA vaccine (from BioNtech/Pfizer or Moderna). The score of the test ranges from less than 0.4 to more than 250. A seronegative score is less than 0.8. Healthy individuals typically score well above 100.

The results show that one quarter of blood cancer patients were seronegative after being fully vaccinated against COVID-19, but these results vary by cancer type. Treatment with drugs that deplete immune system B-cells also reduces immune response to vaccination. This includes BTK inhibitors such as ibrutinib, anti-CD20 antibodies, or combinations of these therapies or their use with venetoclax, a BCL2 inhibitor

These results do not mean blood cancer patients should skip vaccination. Although some patients with hematologic malignancies will not mount a full antibody response compared to healthy individuals, vaccines are safe, and offer protection to the majority, but not all cancer patients. In addition, the antibody response to the vaccine is only part of the story. LLS and others are studying the response of another branch of the immune system: the T-cell response. Vaccines may induce T-cell activation even in some patients that have deficient antibody production.

The best strategy for blood cancer patients, who are an increased risk of serious outcomes and death from COVID-19, is to Get Vaccinated, Act Unvaccinated i7.t.hubspotemail.net/e2t/t...

by layering on additional precautions like wearing a mask, social distancing, and avoiding crowds and poorly ventilated indoor spaces to stay safe from COVID.

Here is a summary of our findings.

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We will continue to update these results as more data is collected and analyzed.

We have also analyzed vaccine response among the small number of Registry participants who have been treated with groundbreaking CAR T-cell immunotherapy, which harnesses the power of their own immune system to fight cancer. Six of seven patients who received CAR-T for CLL, diffuse large B cell or follicular lymphoma were seronegative after vaccination. This is likely due to elimination of normal B-cells by the therapy. In contrast, four of five patients who received a different type of CAR-T for multiple myeloma produced robust antibodies.

The registry is actively seeking additional CAR-T patients to increase the strength of its data.

The work of The LLS Patient Registry continues. In addition to measuring antibody response to vaccination, the Registry recently launched an invitation-only follow-up study evaluating T-cell immune response in a subset of patients from the larger study. We will continue to update you as information becomes available.

On behalf of LLS, thank you for becoming a citizen scientist and helping us fulfill our mission to improve the quality of life of blood cancer patients and their families. We are, as always grateful for your support.

Sincerely,

Gwen Nichols, M.D. Larry Saltzman, M.D.

Chief Medical Officer, LLS Executive Research Director, LLS

Below is a summary of our findings. We will continue to update these results as more data is collected and analyzed.

COVID-19 Vaccine Response by Blood Cancer Diagnosis

Percent of patients with detectable antibodies

Smoldering multiple myeloma 100

Hairy cell leukemia 100

Hodgkin lymphoma 98

Chronic myeloid leukemia 97

Myelodysplastic syndrome/myeloproliferative neoplasm 97

Multiple myeloma 95

Acute myeloid leukemia 91

Acute lymphocytic leukemia 88

T cell lymphoma 85

Diffuse large B cell lymphoma 79

Non-Hodgkin lymphoma, not specified 79

Follicular lymphoma 78

Waldenstrom’s macroglobulinemia 74

Chronic lymphocytic leukemia 64

Marginal zone lymphoma 62

Mantle cell lymphoma 44

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Percent of patients seronegative

Mantle cell lymphoma 56

Marginal zone lymphoma 38

Chronic lymphocytic leukemia 36

Waldenstrom’s macroglobulinemia 26

Follicular lymphoma 22

Non-Hodgkin lymphoma, not specified 21

Diffuse large B cell lymphoma 21

T cell lymphoma 15

Acute lymphocytic leukemia 12

Acute myeloid leukemia 9

Multiple myeloma 5

Myelodysplastic syndrome/myeloproliferative neoplasm 3

Chronic myeloid leukemia 3

Hodgkin lymphoma 2

Hairy cell leukemia 0

Smoldering multiple myeloma 0

Note: There were smaller numbers of patients in the Registry with blastic plasmacytoid dendritic cell neoplasm (1 patient who was seronegative), Burkitt lymphoma (1 patient with detectable antibodies), primary amyloidosis (2 patients with detectable antibodies), primary CNS lymphoma (1 patient who was seronegative, 1 patient with detectable antibodies), primary mediastinal (thymic) large B cell lymphoma (4 patients, all with detectable antibodies).

Source: The LLS National Patient Registry. Data collected from 1,445 patients who had antibody tests atleast 2 weeks after their second dose of Moderna or Pfizer mRNA vaccine. Data collected March 12 to May 5, 2021

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COVID-19 Vaccine Antibody Response among CLL Patients by Type of Treatment

Treatment within the past 2 years Percent of patients seronegative

None 17

Obinutuzumab 90

Rituximab, acalabrutinib 85

Rituximab, ibrutinib 77

Multidrug therapy w or w/o cytotoxic chemotherapy 71

Obinutuzumab, ibrutinib 70

Obinutuzumab, acalabrutinib 66

Rituximab 63

Acalabrutinib 55

Ibrutinib 48

Ibrutinib, IVIG 40

IVIG 25

Source: The LLS National Patient Registry. Data collected from 1,845 patients with chronic lymphocytic leukemia (CLL) who had antibody tests at least 2 weeks after their second dose of Moderna or Pfizer mRNA vaccine. Data collected March 12 to June 12, 2021

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[BeckyLUSA]

Yes, thought the last table was the most interesting showing the percentages of seronegativity based on treatment type.

If one had not been treated, seronegative was only 17%. Appears that based on this list, Ibrutinib had the lowest seronegative results with 48%. If you added IVIG to it dropped to 40% seronegative and to those untreated except for getting IVIG it was only 25% seronegative. Evidently IVIG does offer a little bit of help.

[gardening-girl]

Thanks Len for posting the summary results. What I don't understand is why LLS/Ciitizens chose to publish in Cancer Cell behind a paywall. I've written to the authors and LLS to point out that many of us may want to read the actual published study.

[Benlewis]

This is great info, thanks for sharing. What I don’t understand though is that they define a seronegative score is anything less than .8 but healthy individuals typically score above 100. I guess they are saying if you score above .8 you have SOME protection from vaccines but it would seem to me that at .8 or even 2 or 3 or 10 you have a tiny fraction of the antibodies that a healthy individual would have. The question I’m left with is how much protection? If a vaccine is 95% effective for a healthy person how effective would it be for someone with a score of .8? Maybe I’m just not understanding what I’ve read?

[Pin57 in reply to Benlewis]

Great questions Benlewis about LLS notes on scores. I especially keyed in on the note, “healthy individuals typically score well above 100”. That one caught my attention as LLS Study Dr Saltzman replied to me back in April that my 100.5 score I had per my LLS Study antibody test #1 was “middle of range” in his words at that time.

So what is meant by “well above 100”? … 200?, 500?, 1000?, … Or >2500? Would be good to know more on what antibodies range exactly is for a “healthy person”?

It’s obvious very early/prelim level results this first report release. Looking forward to more findings and details that hopefully provide answers or some type of reply to your fine questions and much more.

[mantana in reply to Pin57]

A member of my family (healthy - no CLL, no cancer etc.) who had COVID-19 early this year, then was vaccinated with two Pfizer shots - scored above 15000 (yes, fifteen thousand) - which, to my understanding, is extremely high.

[tozer]

Blood Cancer UK, recently posted this statement about the PROVENT trial and indicating that the results will be out shortly.'PROVENT is a trial looking at an antibody treatment made by AstraZeneca called AZD7442, which contains antibodies capable of destroying covid. The PROVENT trial is looking at whether this can offer protection to people if the vaccine doesn’t work and people with cancer are included in this trial. If this treatment is found to be effective, it could be an important option for people with blood cancer. Other antibody treatments similar to the PROVENT drug are also being researched.'

bloodcancer.org.uk/support-...

[JustAGuy]

Thanks for this info. Is there a graph of what were the positive scores, by specific blood cancer? That would be very nice to see as well. My score was 2.8, I am treatment naive, diagnosed 2015. I thought my score was better than I now realize after reading your post.