Can Velcade be given subcutaneously in the arm?

Comment by InpharmD Researcher

As landmark trials for bortezomib did not evaluate pharmacokinetic data via subcutaneous injection in the arm, efficacy and safety of injection at upper arm sites is uncertain, especially in pediatric patients. Published literature, however, reports frequent subcutaneous administration into the arm in clinical practice, resulting in greater tolerability compared to abdominal injections. Additionally, a recent case report (see Table 1) also described routine arm administration without associated adverse events, with reactions limited to abdominal sites, further supporting its use in practice despite limited trial-based data.

Background

Recommendations regarding subcutaneous administration of bortezomib caution to ensure medication is delivered into adipose tissue and not muscle, which is dependent on site selection. Several factors, such as skin thickness and subcutaneous fat, appropriate skinfold technique prior to injection, injection angle, and needle length, play a role in site selection. Nursing management suggestions note that sites should be rotated using common subcutaneous site selection, which include the abdomen, the upper arm, and the upper outer aspects of the thighs; however, it should be noted that upper arm sites were not included in pharmacokinetic studies for subcutaneous bortezomib, and thus efficacy and safety at this injection site remain uncertain. Guidance provided was also specific to adult male and female patients, with no recommendations for pediatric adipose tissue composition. [1]

The phase 3 study for bortezomib did not evaluate subcutaneous administration into the arm, and pharmacokinetic data from administration into the abdomen and thigh cannot be extrapolated to this site of administration. For this reason, an observational survey published in 2015 explored oncology nurses’ opinions regarding subcutaneous bortezomib administration. A 44-question electronic survey was developed, and a total of 43 nurses from 17 clinics in 12 states recorded responses. A total of 98%, 19%, and 53% of nurses reported using the abdomen, thigh, and arm, respectively, for administration of subcutaneous bortezomib. The abdomen and arm were preferred by 88% and 12% of respondents, respectively, which was primarily due less irritation/pain (n= 17, 40%), the presence of more tissue/larger area (n= 15, 35%), ease of access (n= 11, 26%), and patient preference (n= 4, 9%). A total of 72% of nurses believed that patients preferred receiving injections in the abdomen compared to 28% who believed patients preferred injections in the arm. Of note, the abdomen (76%) and arm (24%) were preferred in nonprivate facilities compared to all respondents indicating a preference for abdominal injections in private/somewhat private facilities (p= 0.02). [2]

A 2015 brief communication explored the incidence and severity of injection site reactions (ISRs) following subcutaneous bortezomib administration in 22 Japanese patients with multiple myeloma (age range 46 to 80). Bortezomib, administered subcutaneously at a concentration of 1.3 mg/m², was injected into the upper arm, with the injection sites rotated alternately between the arms. The injections were given at a ~30° angle, and reactions were graded based on the National Cancer Institute Common Toxicity Criteria version 4.0. Out of the 197 total injections administered, grade 1 ISRs occurred in only 3 patients (13.6%), representing 3.0% of the total injections, while no grade 2 or higher ISRs were observed. Grade 0 reactions, such as mild redness, warmth, or itching, were noted after 24.9% of the injections. Importantly, none of the patients with grade 1 ISRs required treatment. Comparison to previous research showed that the incidence of ISRs in this cohort was lower than other documented frequencies, particularly when contrasted with thigh or abdomen administration as demonstrated in a previous report. Additionally, some patients who previously experienced frequent ISRs from abdominal injections encountered no reactions when injections were shifted to the upper arm. The acceptability of the upper arm as an alternative site was further supported by the study’s observation that only 2 of 10 patients with a low BMI (<20.0) experienced injection-site reactions, suggesting that upper arm administration offers a viable option even for patients with less adipose tissue. [3]

References:

[1] Kurtin S, Knop CS, Milliron T. Subcutaneous administration of bortezomib: strategies to reduce injection site reactions. J Adv Pract Oncol. 2012;3(6):406-410. doi:10.6004/jadpro.2012.3.6.8
[2] Martin JR, Beegle NL, Zhu Y, Hanisch EM. Subcutaneous Administration of Bortezomib: A Pilot Survey of Oncology Nurses. J Adv Pract Oncol. 2015;6(4):308-318. doi:10.6004/jadpro.2015.6.4.2
[3] Ohgiya D, Tsuchiya T, Suyama T, et al. An acceptable incidence of infusion site reactions after subcutaneous bortezomib administration in the upper arm in Japanese patients with multiple myeloma. Acta Haematol. 2015;133(1):29-30. doi:10.1159/000362587

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Can Velcade be given subcutaneously in the arm?

Level of evidence

D - Case reports or unreliable data  Read more→



Please see Table 1 for your response.


 

Clinical Variant of Serpentine Supravenous Hyperpigmentation Following Subcutaneous Bortezomib Injection

Design

Case report

Case presentation

A 73-year-old White man with multiple myeloma presented to clinic for follow-up of asteatotic eczema and a tinea infection. He complained of a pruritic rash that developed four days after his weekly subcutaneous injection of bortezomib. The patient had been receiving subcutaneous bortezomib injections weekly for 29 months, alternating injection sites in a cyclical pattern of right arm, left arm, left lower quadrant, and right lower quadrant. His only reported side effect from therapy had been anemia, and he had achieved good partial remission of his multiple myeloma with this regimen.

On day 0, the patient received a subcutaneous injection of bortezomib in the right lower quadrant. On day 1, he experienced severe pruritus at the injection site, and by day 4, examination revealed a 4 cm non-tender erythematous thin plaque at the injection site that expanded peripherally, tracking over the surrounding superficial veins. The patient was asymptomatic except for mild pruritus that had lessened since onset, and no biopsy was performed given the classic appearance. His next scheduled injection, which would have been in the right arm, was instead administered in the left lower quadrant to monitor for recurrence. On day 1 following this subsequent injection, he again experienced pruritus, though less severe than the prior reaction, and by day 4, physical exam revealed a 3 cm erythematous plaque with peripheral hyperpigmented vessels.

At that time, the right lower quadrant eruption showed resolving erythema with mild hyperpigmentation of the surrounding veins. The patient reported that his symptoms were tolerable and did not require treatment or dermatology follow-up. He continued subcutaneous bortezomib weekly for nine additional months until his unexpected death at home.

Study Author Conclusions

We believe that this subcutaneous variant of serpentine supravenous hyperpigmentation (SSH) is caused by the same cytotoxic mechanism as cutaneous SSH. The patient’s symptoms of pruritus resolved within 12 days of the bortezomib injection without any treatment. The hyperpigmentation had already begun fading 12 days following the injection. We believe the hyperpigmentation was not progressive. We also believe that this eruption is not commonly reported with subcutaneous bortezomib use due to the ability to rotate injection sites. The prognosis remained benign and self-limited in this patient.

References:

Richards M, Weis SE. Clinical Variant of Serpentine Supravenous Hyperpigmentation Following Subcutaneous Bortezomib Injection. HCA Healthc J Med. 2024;5(6):727-731. Published 2024 Dec 1. doi:10.36518/2689-0216.1708