Response to SARS-CoV-2 vaccination in patients with Multiple Myeloma using a 12-week spaced dosing strategy

Background Evaluating the degree of protection afforded to multiple myeloma (MM) patients by vaccination against SARS-CoV-2 is of critical importance due to the high morbidity and mortality associated with infection and the immunosuppression associated with MM and its treatment. We have previously reported antibody results after first vaccine dose in the UK (which adopted a 12-week spacing strategy between doses); 52 of 93 patients (55.9% [95% CI 45.8, 66.0%]) tested positive for SARS-CoV-2 IgG antibodies (Lancet Haematol 2021). Here we report results after the second dose. Methods Patients who had received two doses of vaccine and had a documented SARS-CoV-2 anti-S IgG antibody test (Ortho Clinical Diagnostics, USA) ≥10 days after the second vaccination were included. Baseline data included disease characteristics, baseline blood tests, MM assessments and treatments (closest prior to first vaccination), vaccination type and antibody status (prior to vaccination, after first vaccination and after second vaccination). Results Sixty-nine patients had documented antibody status after second vaccination. The median age of patients was 67 years (range 47-87) and 41/69 (59.4%) were male. Patients had received a median of 1 prior line of therapy (range 0-8) and 49/69 (71.0%) were on therapy at the time of first vaccination. Of the 69 patients, 58 (84.1% [95% CI 75.5, 92.7%]) tested positive for SARS-CoV-2 IgG post second vaccine (median days between second vaccine and antibody test 26, range 10-85). The 11 patients negative for antibodies after second vaccine dose had all been negative after first vaccine dose. Of the 58 patients positive after second vaccine dose 38 had been positive and 20 negative after first dose. After second vaccination there was no difference in the percentage of patients with a positive result between those who received the Pfizer (30/35, 85.7%) and AstraZeneca (28/34, 82.4%) vaccine, nor was there a difference with sex or age. Patients who had fewer prior lines of therapy were more likely to have a positive antibody result (0-1 prior lines 41/45, 91.1% vs >1 prior line 17/24, 70.8%, p=0.04). There was no significant difference between antibody status for patients on any current therapy or different individual therapies (including anti-CD38 antibodies), although some subgroups were small. Of note, all six patients who had been transplanted ≤12 months ago were antibody positive after the second vaccine dose. Conclusion The majority of patients (84.1%) were positive for SARS-CoV-2 IgG antibodies after second vaccine dose, although the degree and duration of protection from infection afforded by this requires further study. A subset of patients had no measurable response and this was significantly associated with heavily pre-treated MM. It is critical that these patients are closely monitored as they may remain vulnerable to severe infection with SARS-CoV-2 and require additional protective or therapeutic strategies.