SUMMARY  

• Currently, there are no clinical trials designed to evaluate the efficacy and safety of DARZALEX intravenous (IV) or DARZALEX FASPRO subcutaneous (SC) when used concomitantly with IV immunoglobulin (IVIG) therapy.
• Data from the DARZALEX + DARZALEX FASPRO clinical studies show that IVIG was administered concurrently in patients treated with DARZALEX or DARZALEX FASPRO, however no data is available on the efficacy or safety of the combination.^1-6
• Lim et al (2023)⁷ conducted a retrospective chart review of the rates of all grade infections in patients with multiple myeloma who started DARZALEX or bispecific antibodies (BsAB) during time periods of being “ON IVIG” vs “OFF IVIG”.
  • Compared to DARZALEX based therapy BsAB therapy had a higher all grade infection rate, 1.39 (0.91-2.03) vs 2.86 (2.23-3.62) per person years (IRR, 2.06; 95% CI, 1.30-3.38; P=0.001), respectively.
  • All grade infections rates were lower in the ON IVIG arm vs the OFF IVIG arm, respectively, 1.54 (95% CI, 1.07-2.15) vs 2.56 (1.95-3.29) per person years (IRR, 0.60; 95% CI, 0.39-0.93; P=0.016).
• Lancman et al (2020)⁸ presented the rates of infections while on and off IVIG replacement therapy through a retrospective analysis.
  • The annualized rate of infections ‘ON IVIG’ was 1.21 vs 1.96 ‘OFF IVIG’ (incidence rate ratio [IRR], 0.61; 95% CI, 0.45-0.83; P=0.0015). A total of 54 grade 3/4 infections had been reported, with an annual rate of 0.20 ‘ON IVIG’ vs 0.71 ‘OFF IVIG’ (IRR, 0.28; 95% CI, 0.15-0.55; P=0.0002).
• A case report has been identified and included in the reference section for your information.⁹

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

Clinicial data

Lim et al (2023)⁷ conducted a retrospective chart review of the rates of all grade infections in patients with multiple myeloma who started DARZALEX or BsAB during time periods of being “ON IVIG” vs “OFF IVIG”.

Study Design Methods

• Patients who received treatment at St Vincent’s Hospital Melbourne from January 2021 to December 2022 were included in the chart review.
  • The evaluation period ranged from the patient’s initial dose of DARZALEX or BsAB until 28 June 2023.
• Time periods were defined as the following:
  • ON IVIG was any time ≤30 days of last IVIG administration.
  • OFF IVIG was any time >30 days from last IVIG administration.
• Primary outcome: incidence rate of all grade infections (events/person-year) while patients were “ON IVIG” vs “OFF IVIG”.
• Secondary outcome: incidence rate of severe infection (CTCAE Grade 3-5).

Results

Key baseline characteristics

• Out of 52 identified patients, 7 were excluded due to treatment cessation from progressive disease ≤2 months.
• Overall, of the 45 included patients 16 were on DARZALEX.
• Median age was 65 (IQR 59-70) years old and 56% (n=25) were male.
• Median prior lines of therapy received was 1 (IQR 1-3).
• Median time on treatment was 8.94 months (IQR 5.06-14.30).
• A total of 95 all grade infections were identified of which 36% were upper respiratory tract infections, 31% were lower respiratory tract infections, and 12% COVID-19.
• Median time to first infection from start of DARZALEX or BsAB was 3.12 (IQR 1.25-5.61) months.
• In the ON IVIG and OFF IVIG arms, respectively, the rate of severe infections was 0.22 (0.07-0.51) and 0.43 (0.20-0.78) per person years (IRR, 0.52; 0.14-1.66; P=0.234).
  • Of the 15 severe infections, 10 occurred during the OFF IVIG period.

Lancman et al (2020)⁸ conducted a retrospective case-crossover analysis to compare the rates of infections in patients on DARZALEX treatment on and off IVIG replacement therapy.

Study Design Methods

• The analysis retrospectively identified patients with multiple myeloma who received ≥3 IVIG doses during treatment with DARZALEX.
• Time periods were divided as ‘ON IVIG” and ‘OFF IVIG.’
  • ON IVIG was defined as the time within 30 days of the last IVIG administration.
  • OFF IVIG was defined as observation period.
• Each patient was evaluated from the time of the 1^st treatment with DARZALEX to 6 months after the last dose.
• IVIG treatment was initiated at the discretion of the treating physician.
• Primary outcome: annualized rate of infection ON IVIG vs OFF IVIG.
• Secondary outcome: rates of grade 3-5 infections.

Results

Key baseline characteristics

• Overall, 43 patients were included.
• Of the cytogenetics patients (n=39), 46% (n=18) were in the high-risk cytogenetic group.
• Median prior lines of therapy: 2 (range, 0-9).
• Median number of infections in 12 months prior to DARZALEX treatment: 2 (range, 0-6).
• Of the patients evaluated, 88% (n=38) were on concurrent therapies while 12% (n=5) were on single agent DARZALEX.
• Median proportion of days ON IVIG: 35% (range, 8-93%).
• Median time to 1^st infection on DARZALEX 2.5 months (range, 0.1-18.7).
• A total of 176 infections were reported while on DARZALEX treatment. Of those 38% were microbiologically confirmed. Of these reported infections, 56% were viral, 42% bacterial, and 2% fungal.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 27 March 2024.