SUMMARY

• Please contact Janssen for information on the concomitant use of DARZALEX/DARZALEX FASPRO with COVID-19 vaccines.
• Data regarding the number of patients who received concomitant vaccines are presented from the following studies of DARZALEX:
  • MAIA^1,2: 107 (14.5%) patients with newly diagnosed multiple myeloma (NDMM)
  • ALCYONE^3,4: 22 (3.1%) patients with NDMM
  • CASSIOPEIA^5-8: 53 (4.9%) patients (Part 1) and 229 (25.9%) patients (Part 2) with NDMM
  • CASTOR^9,10: 17 (3.4%) patients with relapsed or refractory multiple myeloma (RRMM)
  • POLLUX^11,12: 49 (8.6%) patients with RRMM
  • SIRIUS^13,14: 9 (7.3%) patients with RRMM who had received ≥3 prior lines of therapy or were double refractory (i.e., refractory to both a proteasome inhibitor [PI] and an immunomodulatory imide drug [IMiD])
• Data regarding the number of patients who received concomitant vaccines are presented from the following studies of DARZALEX FASPRO:
  • APOLLO^15,16: in patients with RRMM, 4 (2.67%) patients who received pomalidomide and dexamethasone (Pd), 4 (2.68%) patients who received DARZALEX-Pd, and 4 (2.82%) patients who received DARZALEX FASPRO-Pd
  • PLEIADES^17-19: 12 (18.2%) patients with RRMM in the DARZALEX FASPRO + carfilzomib + dexamethasone (D-Kd) arm, 2 (3%) RRMM patients in the DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone (D-VRd) arm, 9 (13.4%) NDMM patients in the DARZALEX FASPRO + bortezomib + melphalan + prednisone (D-VMP) arm, and 4 (6.2%) NDMM patients in the DARZALEX FASPRO + lenalidomide + dexamethasone (D-Rd) arm. Vaccination with live attenuated vaccines were prohibited in the study.²⁰
  • COLUMBA^21,22: 18 (3.5%) patients with MM who had received ≥3 prior lines of therapy or were double refractory (i.e., refractory to both a PI and an IMiD)
  • ANDROMEDA^23,24: 26 (6.8%) in newly diagnosed patients with systemic light chain (AL) amyloidosis  
• Frerichs et al (2020)²⁵ investigated whether patients receiving DARZALEX produced antibody titers following vaccination with non-live attenuated vaccines. Correlation between these results and safety and efficacy of vaccination is not fully understood.
  • No difference in response rates (development of antibody titer) following Streptococcus pneumoniae and Haemophilus influenzae type B vaccination were observed between DARZALEX-treated (68.8% and 66.7%, respectively) and DARZALEX-naïve patients (55.6% and 62.5%, respectively; P=0.509 and P=0.842).
  • During follow-up (median, 17 months; range, 6-21), 14 out of 17 DARZALEXtreated and 6 out of 10 DARZALEX-naïve patients presented with infectious complications.
  • One DARZALEX-treated patient presented with pneumonia caused by H. influenzae type B. This patient did not develop protective antibody titers against H. influenzae following vaccination. The infection completely resolved with antibiotic treatment.
  • None of the other infections were caused by S. pneumoniae or influenza.
• Other relevant literature describing the concomitant use of DARZALEX/DARZALEX FASPRO with vaccines are referenced in addition to the data summarized below.²⁶

PRODUCT LABELING

• DARZALEX (daratumumab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.

CLINICAL DATA

DARZALEX in Combination with Lenalidomide and Dexamethasone in NDMM

MAIA (MMY3008; clinicaltrials.gov identifier: NCT02252172) is an international, phase 3, randomized, open-label, active-controlled, multicenter study comparing DARZALEX, lenalidomide, and dexamethasone (D-Rd) in patients with NDMM not eligible for high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT; N=737).¹

Results

• Overall, 107 (14.5%) patients received concomitant vaccines during the study (see Table: Summary of Concomitant Vaccines in the ITT Population in MAIA).²

DARZALEX in Combination with Bortezomib, Melphalan, and Prednisone in NDMM

ALCYONE (MMY3007; clinicaltrials.gov identifier: NCT02195479) is an ongoing, phase 3, randomized, open-label, parallel-group, active-controlled, multicenter study comparing DARZALEX in combination with bortezomib, melphalan, and prednisone (D-VMP) vs bortezomib, melphalan, and prednisone (VMP) in patients with previously untreated MM who are ineligible for HDT with ASCT (N=706).³

Results

• Overall, 22 (3.1%) patients received concomitant vaccines during the study (see Table: Summary of Concomitant Vaccines in the ITT Population in ALCYONE).⁴

DARZALEX in Combination with Bortezomib, Thalidomide, and Dexamethasone in NDMM

CASSIOPEIA (MMY3006; clinicaltrials.gov identifier: NCT02541383) is an ongoing, open-label, 2-arm, multicenter, randomized, phase 3 study evaluating the safety and efficacy of DARZALEX in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) in patients with previously untreated MM who are eligible for HDT and ASCT (N=1,085).^5,6

Results (Part 1)

• Overall, 53 (4.9%) patients received concomitant vaccines during Part 1 of the study (see Table: Summary of Concomitant Vaccines in the ITT Population in CASSIOPEIA [Part 1]).⁷

Results (Part 2)

• Overall, 229 (25.9%) patients in the safety analysis set (N=884) received concomitant vaccines during Part 2 (maintenance phase) of the study (see Table: Summary of Concomitant Vaccines in the Safety Analysis Set in CASSIOPEIA [Part 2]).⁸

DARZALEX in Combination with Bortezomib and Dexamethasone in RRMM

CASTOR (MMY3004; clinicaltrials.gov identifier: NCT02136134) is a multicenter, randomized, open-label, active controlled, phase 3 study that evaluated the safety and efficacy of DARZALEX in combination with bortezomib and dexamethasone (D-Vd) compared to bortezomib and dexamethasone (Vd) alone in patients with RRMM (N=498).⁹

Results

• Overall, 17 (3.4%) patients received concomitant vaccines during the study (see Table: Summary of Concomitant Vaccines in the ITT Population in CASTOR).¹⁰

DARZALEX in Combination with Lenalidomide and Dexamethasone in RRMM

POLLUX (MMY3003; clinicaltrials.gov identifier: NCT02076009) is a randomized, open-label, active-controlled (Rd arm), multicenter, phase 3 study that evaluated the efficacy and safety of D-Rd vs Rd in patients with RRMM (N=569).¹¹

Results

• Overall, 49 (8.6%) patients received concomitant vaccines during the study (see Table: Summary of Concomitant Vaccines in the ITT Population in POLLUX).¹²

DARZALEX Monotherapy in RRMM

SIRIUS (MMY2002; clinicaltrials.gov identifier: NCT01985126) is an ongoing, phase 2 study evaluating DARZALEX monotherapy in patients with MM who have received ≥3 prior lines of therapy including a PI and an IMiD or have disease refractory to both (N=106).¹³

Results

• Overall, 9 (7.3%) patients received concomitant vaccines in the study (see Table: Summary of Concomitant Vaccines in the All-Treated Analysis Population in SIRIUS). Patients received influenza vaccine on study day 34, 36, 167, 181, 316, 344, or 351; 1 patient received pneumococcal vaccine on study day 37.¹⁴

DARZALEX FASPRO in Combination with Pomalidomide and Dexamethasone in RRMM

APOLLO (MMY3013; clinicaltrials.gov identifier: NCT03180736) is an ongoing, phase 3 study evaluating the safety and efficacy of daratumumab in combination with pomalidomide and dexamethasone (D-Pd) vs pomalidomide and dexamethasone (Pd) in patients with RRMM who received ≥1 prior treatment with both lenalidomide and a PI (N=304).¹⁵

Results

• In the safety analysis set, 4 (2.68%) patients treated with DARZALEX-Pd, 4 (2.82%) patients treated with DARZALEX FASPRO-Pd, and 4 (2.67%) patients treated with Pd received concomitant vaccines during the study (see Table: Summary of Concomitant Vaccines in the Safety Analysis Set in APOLLO).¹⁶

DARZALEX FASPRO in Combination with Four Standard-of-Care Treatment Regimens in Patients with MM

PLEIADES (MMY2040; clinicaltrials.gov identifier: NCT03412565) is an ongoing, phase 2, multicenter, open-label study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with 4 standard-of-care treatment regimens in patients with MM. Specifically with:¹⁷

• D-VRd for patients with transplant-eligible NDMM (n=67).
• D-VMP for patients with transplant-ineligible NDMM (n=67).
• D-Rd for patients with RRMM with ≥1 prior line of therapy (n=65).
• DKd in patients with RRMM with 1 prior line of therapy (n=60).

Results

• Overall, 12 (18.2%) patients in the D-Kd arm, 2 (3%) patients in D-VRd arm, 9 (13.4%) patients in D-VMP arm, and 4 (6.2%) patients in D-Rd arm, received concomitant vaccines (see Table: Summary of Concomitant Vaccines in the All-Treated Analysis Population in PLEIADES).^18,19

Non-Inferiority Study of DARZALEX vs DARZALEX FASPRO in RRMM

COLUMBA (MMY3012; clinicaltrials.gov identifier: NCT03277105) is an ongoing, phase 3, randomized, open-label, active-controlled, multicenter study evaluating the efficacy and pharmacokinetics  and infusion-related reactions of DARZALEX vs DARZALEX FASPRO in patients with RRMM.²¹

Results

• Overall, 18 (3.5%) patients received concomitant vaccines in the study (see Table: Summary of Concomitant Vaccines in the Safety Analysis Population in COLUMBA).²²

DARZALEX FASPRO in Combination with Bortezomib, Cyclophosphamide, and Dexamethasone for AL Amyloidosis

ANDROMEDA (AMY3001; clinicaltrials.gov identifier: NCT03201965) is an ongoing, phase 3, randomized, open-label, active-controlled, multicenter study evaluating the efficacy and safety of DARZALEX FASPRO in combination with bortezomib, cyclophosphamide and dexamethasone (VCd) compared with VCd in newly diagnosed patients with systemic AL amyloidosis.²³

Results

• Overall, 26 (6.8%) patients received concomitant vaccines in the study (see Table: Summary of Concomitant Vaccines in the Safety Analysis Population in ANDROMEDA).²⁴

Impact of DARZALEX on the Production Antibody Titers

Frerichs et al (2020)²⁵ investigated the impact of DARZALEX on normal plasma cells in bone marrow samples and whether patients produced antibody titers following vaccination with non-live attenuated vaccines. Correlation between these results and the safety and efficacy of vaccination is not fully understood.

Study Design/Methods

• To evaluate the effect of DARZALEX on antigen-specific antibody responses, 17 RRMM patients were vaccinated against S. pneumoniae and H. influenzae type B during DARZALEX monotherapy.
  • The median duration of DARZALEX treatment at vaccination was 2 months (range, 0.5-17).
  • All patients received dexamethasone as infusion-related reaction prophylaxis.
• Ten DARZALEX-naïve RRMM patients were vaccinated as a control arm.
  • Most patients (80%) were treated with an IMiDbased regimen; the median duration of treatment with current regimen for these patients was 11 months (range, 0-57).
  • All regimens contained low-dose dexamethasone, except for 1 patient who received lenalidomide maintenance without glucocorticoids.
• S. pneumoniae vaccination consisted of the conjugated PCV-13 vaccine (Prevenar, Pfizer) followed by the polysaccharide PPV-23 vaccine (Pneumovax, Merck Sharp & Dohme), both intramuscularly administered with an 8-week interval.
• Specific antibody titers were measured using enzyme-linked immunosorbent assay (ELISA) at baseline, as well as 4 and 8 weeks after each vaccine.
  • Response was defined as an absolute titer ≥2 μg/mL or ≥2-fold increase in 6 out of 9 analyzed pneumococcal subtypes (6B, 8, 9, 14, 15B, 19F, 20, 23F and 33F).
• H. influenzae vaccination consisted of a single intramuscular dose of Act-Hib (Sanofi), and specific antibody titers were assessed using ELISA at baseline, as well as 4 and 8 weeks following vaccination.
  • Response was defined as an absolute titer ≥1 μg/mL, or ≥4-fold increase in titer.

Results

• No difference in response rates following S. pneumoniae and H. influenzae type B vaccinations were observed between DARZALEX-treated (68.8% and 66.7%, respectively) and DARZALEX-naïve patients (55.6% and 62.5%, respectively; P=0.509 and P=0.842).
• In addition, 3 patients (2 DARZALEX-treated and 1 DARZALEX-naïve patient) had protective titers against H. influenzae at baseline and retained immunity. These results are similar to, or better, when compared to those previously reported in less heavily pretreated MM patients.
• In addition, 13 of the 17 DARZALEX-treated patients received trivalent seasonal influenza vaccination during seasons 2016/2017 and 2017/2018.
• Serum samples were collected at baseline, as well as 3 and 12 weeks following vaccination.
  • Seroprotection rates were 31% for H3N2, 38% for H1N1 and 23% for BBrisbane.
  • In addition, 4 patients (31%) developed seroprotective titers against ≥2 strains, of whom 1 patient was protected against all 3 strains.
  • Seroconversion rates were 17% for H3N2, 25% for H1N1 and 17% for BBrisbane.
  • Two patients showed seroconversion for ≥2 strains.
  • Although we did not perform serological analyses in DARZALEX-naïve RRMM patients, prior studies have reported similar response rates.
• During follow-up (median, 17 months; range, 6-21), 14 out of 17 DARZALEX-treated and 6 out of 10 DARZALEX-naïve patients presented with infectious complications.
• One DARZALEX-treated patient presented with pneumonia caused by H. influenzae type B. This patient did not develop protective antibody titers against H. influenzae following vaccination. The infection completely resolved with antibiotic treatment.
• None of the other infections were caused by S. pneumoniae or influenza.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 10 May 2024.

In response to your specific request, summarized in this response are the relevant data from company-sponsored studies pertaining to this topic.