Table 1.

Phase II and phase III vaccination trials in patients with multiple myeloma.

Vaccine	# Of Patients/controls	Schedule	Outcome	Safety	Comments	Author
Influenza
FV trivalent A/Singapore/6/86 (H1N1), A/Wuhan/359/95 (H3N2) and B/Beijing/184/93	MM: 52 patients 16 had chemotherapy <1 week and 7 had high-dose TX + ASCT <6 months prior to vaccination. 21 were on interferon α TIW	One dose	13% developed protective titers against one, 10% against 2, and 19% against all three strains	No AEs reported	Receiving chemotherapy <7 days prior to vaccination correlated with poor response	Robertson et al. [21]
FV trivalent A/California/7/09 (H1N1), A/Texas/50/12 (H3N2), and B/Massachusetts/60/ 08	15 pts with MM out of 36 with hematological malignancies and 70 with solid tumors	72% of all patients received a second vaccination	Protective titers to all three strains increased from 3 to 27%	A second vaccination in pts with no response recommended	Increase in protective titers varied between 3 and 10% dependent on strain	Sanada et al. [22]
FV trivalent A(H1N1)pdm09, iA(H3N2), B/Yamagata-lineage	48 pts with SMM or MM	50%	Protective titers to all three strains. 0 at baseline, 14% after first and 31% after second vaccination	A second vaccination in pts with no response recommended	Increase in protective titers varied between 18 and 44% dependent on strain	Hahn et al. [23]
Herpes zoster
VZV gamma-irradiation inactivated	Scheduled for ASCT hematologic malignancies: 560/106 MM: 244/50 History of HVZ infection and/or antibodies to VZV	Four doses, first dose 5–60 days before ASCT, thereafter 30, 60, and 90 days after ASCT, or placebo	8 vs. 21% had HZV reactivation during 2.3–2.4 years FU	Proportion of individuals with injection site AEs 29 vs. 7%; General SAEs 33 vs. 33%	Patients had acyclovir or valaciclovir prophylaxis for 3 or 6 months after ASCT	Winston et al. [37]
Adjuvanted recombinant zoster glycoprotein E vaccine (Shingrix®)	Hematologic malignancies (excluding CLL on oral therapy) receiving or having just finished immunosuppressive TXT: 286/283 MM: 67/65	Two doses, 1–2 months apart, or placebo	VZV reactivation in 2 vs. 14 patients 80.4 vs. 0.8% had antibody response to glycoprotein E. Humoral and cellular immune response persisted at months 13	Proportion of individuals with pain at the injection site: 79.5 vs. 16.4%, fatigue: 58.3 vs. 27.2%; general SAEs 23.3 vs. 29.4%	Antiviral prophylaxis according to standards of participating centers Vaccine efficacy 87.2% 30.2% were excluded from per protocol group from immune response evaluation, short follow-up	Dagnew et al. [39]
Pneumococci
PCV13	SMM: 20	One dose	60% responders after 1 month, 35% after 6 months, and 25% after 12 months	Not reported	40% had a positive opsonophagocytic test after 1 month, 30% after 6 months, and 25% after 12 months	Bahuad et al. [52]
PCV13	MM: 7 Controls: 18	One dose	IgG response in MM: 23.3% vs. 25.7% in controls	Not reported	Response 6 months after vaccination, MM: 14.3%, controls: 25.7%	Mustafa et al. [55]
PCV7 or PPV23 (1:1 randomization)	MGUS: 15 MM: 15, 11 of them on active therapy Waldenströms disease: 15, 1 on active therapy Controls: 20	Half received single dose of PCV7 or PPV23	IgG and particularly IgM antibodies were significantly lower in MM	Not reported	Opsophagocytic activity correlated with IgG antibody levels in MGUS and controls, but not in MM, and Waldenström’s disease	Karlsson et al. [57]
PPV23	MM: 60 pts vaccinated before ASCT Pts with preexisting high antibody levels were excluded	One dose	Response in 33% Response rate higher (73%) in pts with CR	No SAEs observed	Correlation with disease control and antibody response	Hinge et al. [54]
PPV23 (Pneumovax II)	MM: 52 patients 16 had chemotherapy <1 week and 7 had high-dose TX + ASCT <6 months prior to vaccination. 21 were on interferon α TIW	One dose	Response in 40% Fourfold increase in specific antibodies was recorded: 56%.	No SAEs observed	Poor antibody response was associated with higher sepsis risk	Robertson et al. [21]
PCV13 and PPV23	MM: 20 pts scheduled for induction TX Median time between both vaccinations: 21 days	One dose of PCV13 and PPV23 each	Protective IgG response in 60% antipneumococcal serum levels of IgG. IgG2, IgM, and IgA increased by 5.1-, 5.9-, 1.5-, and 3.8-fold	Not reported	Antibody levels decreased significantly at follow-up (28–502 days) in pts without ASCT but was even more pronounced in those receiving ASCT	Renaud et al. [72]
Haemophilus influenzae
Haemophilus influenza type B	MM: 52 patients 16 had chemotherapy <1 week and 7 had high-dose TX + ASCT <6 months prior to vaccination. 21 were on interferon α TIW	One dose	Pre-vaccination protective ab titers: 45% Postvaccination: 75%, fourfold increase in ab titers in 41	No SAEs reported by patients	Receiving high-dose therapy and ASCT <6 months prior to vaccination correlated with poor response	Robertson et al. [21]