Re-vaccination following ASCT in MM patients receiving lenalidomide maintenance

Current guidelines of the American Society of Blood and Marrow Transplantation (ASBMT), European Society for Blood and Marrow Transplantation (EBMT), and the Infectious Disease Society of America (IDSA) strongly advise that re-vaccination should start between 6–12 months after autologous hematopoietic stem cell transplantation (ASCT), with a set schedule. Additionally, the guidelines recommend that Multiple Myeloma (MM) patients on active therapy should not be vaccinated.

However, some centers differ in their practice for MM patients on maintenance therapy and do not immunize at all. As MM patients are more susceptible to infections until immune reconstitution, re-immunization after ASCT has been seen as necessary to ensure their wellbeing. To better understand the safety and efficacy of revaccinating MM patients during maintenance therapy, a study was conducted by Meighan Palazzo and colleagues, from the Memorial Sloan Kettering Cancer Center (MKSCC) in New York, and was published in the December 2017 edition of Biology of Blood and Marrow Transplantation, to specifically examine the safety and efficacy of revaccinating MM patients receiving lenalidomide maintenance (LM) after ASCT.

A continuous low dose LM is standard of care for MM patients as it prolongs progression free survival (PFS) and overall survival (OS). MM patients who underwent their first ASCT between 2010–2014 at the MSKCC less than 1 year after diagnosis and did not receive a tandem transplant, were vaccinated (1-year post ASCT) with the following vaccines: haemophilus influenzae type B conjugate vaccine (HiB); poliovirus inactivated vaccine (IPOL); pneumococcal conjugate vaccine (Prevnar 13-Valent) and tetanus/diphtheria/pertussis (Tdap) at a three dose series at 1–3 months intervals; hepatitis A-hepatitis B vaccine (Twinrix) (three-dose series at 0, 1 and 6 month intervals) and measles, mumps, and rubella (MMR) (two-dose series at 2–3 months intervals). Patients were classified as ‘immune’ if pre-titers were within the defined cut-offs for protection and post-titers continued to demonstrate immunity.

Results:

• Patients (pts) on lenalidomide maintenance (LM) vs those not receiving LM: 91 pts vs 31 pts
  • Median age: 58 years (range, 42-75) vs 57 years (range 38-71)
  • Lenalidomide included in the induction therapy: 79% vs 65%
• Response by vaccine subtype (responder vs non-responder vs immune):
  • Haemophilus influenzae type B conjugate vaccine: 71% vs 1.7% vs 24%
  • Pneumococcal: 58% vs 42% vs 0%
  • Polio: 26.6% vs 0% vs 68.8%
  • Tetanus: 64% vs 3% vs 32%
  • Diphtheria: 70% vs 24.4% vs 0%
  • Pertussis: 76% vs 7.5% vs 13%
  • Hepatitis A: 30% vs 21% vs 29%
  • Hepatitis B: 40% vs 41% vs 3%
• Rates of live vaccinations were much lower in this study
• Nine pts retained immunity to measles, while three and seven pts retained immunity to MMR, respectively (although post-MMR titers were not available for the majority, and therefore, it was not possible to evaluate response)
• No pts contracted illnesses after immunization
• No statistical difference in the rate of response was observed for pts receiving LM vs those who were not for HiB (P>0.95), pneumococcus (P=0.1), tetanus (P=0.56), diphtheria (P=0.31), pertussis (P>0.95), Hep A (P=0.66), or Hep B (P=0.78)

This study concludes that efforts should be made to vaccinate MM patients on LM after ASCT in order to offer immunity to preventable diseases. In addition, it showed that the response rates to the majority of vaccines are high and are not affected by the use of LM. Additionally, data from this study was similar to previously published studies of vaccine responses after ASCT. It has also been found that the retention of immunity prior to vaccination varies based on the infectious agent, for example, patients tend to retain immunity to polio and diphtheria while patients did not retain immunity to pneumococcus. An important observation made during this study is that there was no vaccine-related AEs, suggesting this approach is both safe and effective. Future studies will examine the optimal timing of vaccination.

The limitations of this study include the inclusion of only a small number of patients (in particular small numbers for those in the no LM cohort), a lack of a clear definition for immunocompetence after ASCT and potential subjectivity over the chosen cut-off for a given titer response. However, this study highlights the importance of patient management during treatment and ties in with a key abstract presented at ASH 2017, in which it was shown that benefit was gained by a double flu vaccination strategy for MM patients, which could save lives – see previous MM Hub article.