Subcutaneous Daratumumab for Multiple Myeloma: Applying the Lessons from Clinical Trials to Clinical Practice

TLG1866-1

With commentaries by
Tiffany Richards, MS, ANP, AOCNP
Advanced Nurse Practitioner
M.D. Anderson Cancer Center,
Houston, TX

Each year in the United States, more than 32,000 people are diagnosed with multiple myeloma, with almost 13,000 dying of the disease.¹ Over the past 4 decades, the 5-year survival rate for patients with multiple myeloma has more than doubled, from 24.6% to 52.4%, representing significant medical advancements.² Nonetheless, most patients face shortened life expectancy with a disease that remains largely incurable.³ Despite these challenges, leading experts suggest that new and emerging therapies will further improve the prognosis for a number of individuals, among whom myeloma will become a chronic disease that is manageable with long-term, continuous therapy.^4,5 In this setting, health-related quality of life must be seriously considered along with survival benefits, which means that such factors as drug toxicity and convenience of administration become increasingly important.⁵

For patients with relapsed or refractory multiple myeloma, leading experts recommend daratumumab—a CD38-directed monoclonal antibody that was first approved by the US Food and Drug Administration (FDA) in 2015.^6-8 Over the past 5 years, FDA approvals for daratumumab have expanded from the heavily pretreated population to include newly diagnosed, transplant-eligible patients.⁹

Along with an expanded list of indications for daratumumab, methods for administration of the agent have evolved as well. When initially approved, the median duration of first intravenous (IV) infusion of daratumumab was approximately 7 hours, with some infusions lasting for >10 hours.¹⁰ Subsequent trials showed that split dosing could decrease infusion times to 3 or 4 hours, with some patients able to safely receive rapid infusions over 90 minutes.^11-13 In 2020, time-saving advances took a giant step forward with the approval of a subcutaneous (SC) formulation of daratumumab, which reduced the administration time to just 3 to 5 minutes, while maintaining safety and efficacy.^13,14

This publication provides a clinical review of SC daratumumab, including indications and appropriate use, pivotal clinical trial data, management of adverse events (AEs), and strategies for patient education. At the conclusion of each section, Tiffany Richards, MS, ANP, AOCNP, Advanced Practice Nurse, University of Texas M.D. Anderson Cancer Center, Houston, TX, offers practical insights to help nurses bridge the gap from clinical trials to clinical practice.

Appropriate Use of Subcutaneous Daratumumab in Patients with Multiple Myeloma

Daratumumab is approved in the United States for the treatment of patients with multiple myeloma.⁸ Monotherapy with daratumumab is indicated for patients who have received ≥3 prior lines of treatment that included an immunomodulatory drug (IMID) and a proteasome inhibitor (PI), or for those who are double-refractory to an IMID and a PI.⁸ Specific combination therapies with daratumumab are approved for a variety of patient subgroups, with protocols depending on previous treatments and transplant eligibility (Figure 1).¹⁵

Daratumumab should be administered according to protocol guidelines, with administration intervals ranging from weekly to monthly.⁸ Unlike IV daratumumab, which is dosed based on a patient’s body weight, SC daratumumab is flat-dosed at 1800 mg plus 30,000 units hyaluronidase in a 15-mL injection volume.^8,15 The hyaluronidase speeds dispersion and absorption in the SC space.^16,17 Patients should receive pre-injection medications 1 to 3 hours before administration, including an IV corticosteroid, an oral antipyretic, and an oral or IV antihistamine.⁸ Following the injection, patients should be given an oral corticosteroid, although some individuals may not require this addition if they are already receiving a corticosteroid as part of a combination regimen.⁸ For patients with a history of chronic obstructive pulmonary disease, short- and long-acting bronchodilators and inhaled corticosteroids may be considered, with discontinuation after 4 uneventful injections.⁸ All patients should begin antiviral prophylaxis for herpes zoster virus reactivation within 1 week of initiating daratumumab therapy and for 3 months after treatment cessation.⁸

Commentary by Tiffany Richards, MS, ANP, AOCNP: At M.D. Anderson, we prescribe acetaminophen, diphenhydramine, montelukast, and famotidine as our premedications. Patients should receive premedications 1 to 3 hours before the injection. Patients should also be prescribed postinfusion steroids to take the day after the infusion.

In patients with a history of lung disease, caution should be exercised. We do pulmonary function studies for these patients, and if their forced expiratory volume in 1 second (FEV1) is between 50 and 80, we order a nebulizer treatment prior to the infusion, to minimize the risk for bronchospasms. We are more cautious about using daratumumab in patients with poor lung function (FEV1 <50), because of the risk for experiencing a severe reaction. Additionally, healthcare providers should consider prescribing a short- and long-acting bronchodilator inhaler to prevent postinfusion reactions in patients with chronic lung disease.

As far as injecting daratumumab subcutaneously, it should be injected at a 45-degree angle to the abdomen, 3 inches from the navel. Additionally, the injection site should be rotated, and the injection should not be given in an area with bruising or that is sore. Some nurses may need to get used to applying constant pressure over 5 minutes, because it can be uncomfortable on the palm of the hand. Alternatively, nurses may consider injecting a little bit, resting, injecting a little bit more, and so on. If the patient reports pain with the injection, the injection should be stopped and given over a longer period. For practitioners who are not experienced in administering higher volume SC injections, it is key for clinical nurse educators to demonstrate the technique. Patients should be monitored for several hours after the injection, for the first few doses.

Pivotal Clinical Trials with Subcutaneous Daratumumab

The FDA approval of SC daratumumab was based on results of 2 pivotal clinical trials: the phase 2 PLEIADES trial and the phase 3 COLUMBA trial.¹⁸

COLUMBA Phase 3 Trial: SC versus IV Daratumumab. The COLUMBA trial was an open-label, noninferiority, monotherapy study that involved 522 patients with relapsed or refractory multiple myeloma who had received ≥3 prior lines of therapy, including an IMID and a PI, or who were double-refractory to an IMID and a PI.¹³ Exclusion criteria included the receipt of autologous stem-cell transplant within 12 weeks prior to study randomization. ¹³ Patients were randomized in a 1:1 ratio to receive either 1800 mg of SC daratumumab coformulated with 2000 U/mL recombinant human hyaluronidase PH20 or 16 mg/kg of IV daratumumab.¹³ Treatments were administered once weekly for 2 cycles, every 2 weeks for 4 cycles, and every 4 weeks thereafter, until disease progression or toxicity.¹³ The coprimary end points were maximum trough concentration of daratumumab and overall response rate.¹³ Safety data were also reported.¹³

After a median follow-up of 7.5 months, SC daratumumab was found to be noninferior to the IV formulation. ¹³ The overall response rate in the SC group was 41%, compared with 37% in the IV group, with no statistically significant difference reported between the groups (odds ratio, 1.19; 95% confidence interval, 0.83-1.69).¹³ Maximum trough concentrations were also similar between the groups, at 593 μg/mL and 522 μg/mL with the SC and IV formulations, respectively.¹³ These findings led the investigators to conclude that the 2 formulations had similar efficacy and pharmacokinetics.¹³

Safety profiles were also similar between the groups, with 88% of patients in the SC group reporting ≥1 treatment- emergent AEs (TEAEs), compared with 89% in the IV group.¹³ Approximately half of all patients in both the SC group (46%) and the IV group (49%) experienced ≥1 grade 3 or higher TEAEs, further supporting a similar safety profile (Figure 2).¹³

The most common grade 3 or 4 TEAEs included anemia, thrombocytopenia, and neutropenia—the latter of which occurred more frequently in the SC group.¹³ Slightly more than one-fourth of the patients experienced serious AEs, at a rate of 26% in the SC group and 29% in the IV group, with pneumonia being the most common.¹³ One treatment-related death was reported in the SC group, compared with 4 in the IV group.¹³

Although safety profiles were generally similar between the groups, the SC formulation was associated with fewer infusion-related reactions and thus fewer infusion- related treatment modifications (Table 1).¹³ Approximately one-third (34%) of patients in the IV group experienced an infusion-related reaction, compared with 13% in the SC group.¹³ The most common infusion- related reactions (SC vs IV) were chills (5% vs 12%, respectively), pyrexia (5% vs 3%, respectively), and dyspnea (1% vs 7%, respectively).¹³

In the IV group, infusion-related reactions led to dose interruptions in 31% of patients, whereas 10% of patients required an infusion rate decrease, 2 patients needed to discontinue treatment, and 1 patient required infusion termination. In sharp contrast, no treatment modifications due to infusion-related reactions were needed in the SC group.¹³ Although infusion-related reactions were less common with SC administration, a small number of patients (n = 18; 7%) in the SC group did experience an injection-site reaction, most often erythema (n = 4). All of the injection-site reactions were mild, and none required treatment discontinuation.¹³

Throughout the duration of the COLUMBA trial, >88% of patients responded to the Cancer Therapy Satisfaction Questionnaire, which revealed a consistently more positive perception of and greater satisfaction with therapy in the SC group than in the IV group.¹³ Patients in the SC group were more often satisfied with the form of cancer therapy, the difficulty of their treatment relative to their expectations, and the side effects they experienced.¹³

PLEIADES Phase 2 Trial: SC Daratumumab in Combination with Standard Treatment Regimens. In contrast to the COLUMBA trial, which compared SC versus IV daratumumab as monotherapy, the phase 2 PLEIADES trial investigated the safety and efficacy of SC daratumumab in combination with standard treatment regimens.¹⁹ PLEIADES enrolled a total of 199 patients with multiple myeloma, of whom 67 were newly diagnosed and transplant-eligible, 67 were newly diagnosed and transplant-ineligible, and 65 had relapsed or refractory multiple myeloma with ≥1 prior lines of therapy.¹⁹ In addition to daratumumab, newly diagnosed, transplant-eligible patients received bortezomib, lenalidomide, and dexamethasone; newly diagnosed, transplant-ineligible patients received bortezomib, melphalan, and prednisone; and patients with relapsed or refractory multiple myeloma received lenalidomide and dexamethasone.¹⁹

The primary efficacy end points included overall response rate (ORR) in newly diagnosed, transplant-ineligible patients and patients with relapsed or refractory multiple myeloma, and very good partial response or better (≥VGPR) in newly diagnosed, transplant-eligible patients.¹⁹ Safety analysis focused on TEAEs and infusion- related reactions.¹⁹

The primary efficacy end points were met for all 3 groups (see Table 2).¹⁹ The ORR rates were 88.1% and 90.8% in newly diagnosed, transplant-ineligible patients and patients with relapsed or refractory multiple myeloma, respectively. Among newly diagnosed, transplant-eligible patients, the ≥VGPR rate was 71.6%.¹⁹ Regarding secondary end points, the ≥VGPR rates for transplantineligible patients and patients with relapsed or refractory multiple myeloma were 64.2% and 64.6%, respectively, whereas the ORR rate was 97% in the transplant-eligible population.¹⁹ These outcomes were similar to those described in published data on IV daratumumab.²⁰

Safety data on SC daratumumab were also comparable to historical data on IV daratumumab regimens.¹⁹ Grade 3 or 4 TEAEs occurred in 58.2%, 68.7%, and 78.5% of patients in the transplant-eligible, transplant- ineligible, and relapsed or refractory multiple myeloma groups, respectively.¹⁹ Infusion-related reactions of any grade were slightly less common with SC administration in the PLEIADES trial (7.5%) compared with the COLUMBA trial (13%), whereas injection-site reactions were almost the same, at 7.5%, versus 7% in PLEIADES and COLUMBA, respectively.^13,19

Pivotal Clinical Trial Conclusions. Collectively, the findings from the COLUMBA and PLEIADES trials supported comparable safety and efficacy of SC daratumumab versus IV daratumumab in both monotherapy and combination settings. In transitioning from the IV to the SC formulation, nurses should expect to see significantly fewer infusion-related reactions, although they should remain aware that mild injection-site reactions may occur in approximately 7% of patients.^13,19

Commentary by Tiffany Richards, MS, ANP, AOCNP: The safety profiles of IV and SC daratumumab are similar. With SC use, nurses may see injection-site reactions, which typically involve mild erythema or bruising at the injection site. For those nurses who have administered bortezomib subcutaneously, the injection-site reaction with daratumumab is similar to what is observed with bortezomib.

It is also important for nurses to be aware that systemic administration-related reactions can be a bit more delayed with SC daratumumab. Instead of reactions occurring in 1 to 2 hours, as they do with IV infusion, they may take 3 to 4 hours to develop after SC injection, so patients will need to be monitored for several hours to ensure that they do not experience a delayed reaction.¹³ As with IV daratumumab, practitioners need to be especially vigilant with the first SC injection, as this is when reactions are most likely to occur.¹³

When educating patients, I inform them about the signs of a reaction, such as nausea, shortness of breath, fever, chills, runny nose, or nasal congestion. Nurses should remember that patients may not be aware of a reaction when it is occurring; a lot of patients are used to having nausea, or they may just attribute a runny nose to allergies. Therefore, I also tell patients to let a nurse know if they feel anything different at all. That way, a nurse can intervene before a more severe reaction occurs. Another benefit to SC administration is that there is no additional fluid volume, which will be especially beneficial for patients who have cardiomyopathy or who are more prone to getting fluid overload, because with IV daratumumab, they receive at least 500 mL of fluid.

Beyond Systemic Administration-Related Reactions: Clinical Management of Adverse Events Associated with Daratumumab Combination Therapy in the Relapsed and Refractory Setting

In addition to the reduced risk for infusion-related reactions with SC daratumumab, which can be partially mitigated with appropriate pretreatment and posttreatment medications, nurses should remain aware of other AEs that may occur, as well as the possibility of daratumumab- associated effects on laboratory values.

According to leading experts, the greatest usage of SC daratumumab is likely to be for the treatment of patients with early relapsed multiple myeloma, usually in combination with bortezomib and dexamethasone. ^8,21,22 The benefits of this triplet combination therapy were demonstrated in the phase 3 CASTOR trial, which showed significantly improved progression- free survival in patients with relapsed or refractory multiple myeloma when daratumumab was added to bortezomib and dexamethasone (16.7 months vs 7.1 months with bortezomib and dexamethasone alone; P <.0001).²³

The following describes some of the common AEs that may be reported with this combination, their rates of occurrence in patients in the CASTOR trial, and related strategies for management.

Thrombocytopenia. Almost two-thirds (60%) of patients in the CASTOR trial developed treatment-emergent thrombocytopenia, among whom 77% had grade 3 or 4 thrombocytopenia.²³ If this AE occurs in cycles 1 or 2, it may be attributed to bone marrow involvement with multiple myeloma; thus, platelet transfusion can provide support, but adjustment of therapy is not recommended. In contrast, if thrombocytopenia occurs in later cycles (eg, cycles 5 or 6), it may be a treatment-induced effect, possibly requiring a dose reduction of bortezomib.²² Dose reductions of daratumumab are not recommended.^8,22

Neutropenia. In the CASTOR trial, 1 of 5 patients (20%) developed neutropenia, with 69% of the cases grade 3 or 4.²³ These patients may benefit from receiving the growth factor filgrastim, which can be administered during the weeks that the patients are taking a break from bortezomib.^8,22 Although delaying the next dose of daratumumab may be considered, as noted earlier, dose reductions of daratumumab are not advised.⁸ Additionally, patients with neutropenia should be monitored for signs of infection.⁸

Infectious complications. Approximately one-third (35%) of patients in the CASTOR trial developed an upper respiratory tract infection, although few cases (7%) were grade 3 or 4.²³ Although only 16% of patients developed pneumonia, 66% of the cases were grade 3 or 4.²³ In patients with a history of pulmonary infections, prophylactic antibiotics or gamma globulin should be considered.²² Further, all patients should receive an antiviral agent prophylactically, in order to prevent herpes zoster virus reactivation.^8,22

Peripheral neuropathy. Half of all patients (50%) in the CASTOR trial developed peripheral sensory neuropathy, but only 9% of these cases were grade 3 or 4.²³ If peripheral neuropathy occurs, a bortezomib dose reduction may be needed. In addition, symptomatic therapy can be beneficial, including such oral medications as gabapentin, pregabalin, or tricyclic antidepressants and topical agents such as lidocaine.²²

Diarrhea. Approximately 1 of 3 patients (35%) in the CASTOR trial developed diarrhea, with about 1 of 10 patients (10%) experiencing grade 3 or 4 diarrhea.²³ Standard antidiarrheal medications are recommended for the management of diarrhea in these individuals.²²

Commentary by Tiffany Richards, MS, ANP, AOCNP: Management of treatment-related AEs begins with educating patients as to what they can expect and how to manage symptoms as soon as they develop. For myelosuppression, complete blood count monitoring is essential to mitigate complications. If a patient has neutropenia, then the use of growth factor support can be considered. Management of thrombocytopenia occurs more commonly when daratumumab is administered in combination with other antimyeloma therapies. Patients may require frequent blood count monitoring with transfusion support, particularly those with heavily infiltrated bone marrow.

Infections occur in up to 16% of patients, so patients need to be educated on the prompt reporting of infections, particularly upper respiratory tract symptoms. Prophylactic antibiotics are not recommended, however, in patients with frequent infections. In patients with hypogammaglobulinemia, monthly intravenous immunoglobulin may be beneficial. Patients should be placed on antiviral therapy with either acyclovir or valacyclovir, because of the increased risk for herpes zoster virus reactivation.

Peripheral neuropathy may occur when daratumumab is administered in combination with bortezomib/dexamethasone. Educating patients on what peripheral neuropathy is, how to recognize it, and the importance of prompt reporting are all essential for ensuring early identification and dose reductions of bortezomib.

Daratumumab binds to CD38 present on the surface of red blood cells, which causes interference with the ability to perform cross-matching for blood products. Therefore, it is essential that patients undergo red blood cell antibody testing or type and cross-match prior to the first injection of daratumumab. Patients should be instructed that if they require a blood transfusion, they need to inform the prescribing provider that they are receiving daratumumab.

Subcutaneous Daratumumab: Patient Communication Strategies

As therapeutic options for multiple myeloma have increased over the years, so have clinical decisions that must be made by patients and their healthcare providers. Shared decision-making is a key part of this process²⁴— and one in which nurses play a critical role. Nurses need to couple communication skills with clinical management, patient education, psychological support, advocacy, and outcome evaluation.²⁵ Although a comprehensive review of shared decision-making in oncology is beyond the scope of this article, some practical tips may help nurses guide candidates for SC daratumumab therapy through the decision-making process.

Commentary by Tiffany Richards, MS, ANP, AOCNP: Treatment decision-making in multiple myeloma can be a real challenge for practitioners as well as for patients, because we have so many treatment options.

In patients with relapsing myeloma, providers will determine what type of relapse an individual is experiencing. Are they having a biochemical relapse, or are they progressing with new bone disease? How fast is their myeloma progressing, and what do their cytogenetics show? It is important for patients to understand what we, as providers, are taking into consideration when trying to determine the best treatment options.

From there, what I usually do when I go in with a patient is, I say, “This is what your disease is doing, and because of that, these are the options we have right now.” We discuss the various treatment options and the side-effect profile of each regimen. Then we try to narrow it down a little bit for the patients, because it can be very overwhelming for them if they are just given response rates and side effects and are then asked to choose. Usually, I will say, “This is our first choice, this is our second choice, and these are the reasons why, but if you want to go with these other choices, we can certainly do that.” If a patient chooses a different regimen, that is okay, but they need to understand the risks they may be taking.

Specifically concerning daratumumab, I do not think patients receiving IV infusions will have difficulty transitioning to SC injections, and I do not think SC injections will be an issue for those who are just starting daratumumab, either. I think any time you can give a patient a shorter time in the infusion therapy center, they are going to be happy about it.

Before giving SC daratumumab, the most important piece of information you can provide to patients is what to expect. All patients should be informed that they are going to receive an SC injection, which will be administered over 5 minutes, and that they will feel constant pressure. Usually, the SC route ends up being a nonissue.

Conclusion

As treatments for multiple myeloma become more effective, patients are living longer and therefore undergoing continuous therapy over a longer period of time. In this setting, health-related quality of life is becoming increasingly important in the treatment decision-making process. When daratumumab is selected, SC delivery significantly improves the treatment burden by shortening the infusion time from hours to minutes, while also reducing the rate of systemic administration-related reactions to approximately 11%. Still, infusion-related reactions and injection-site reactions are possible, and nurses must be aware of these potential issues. Nurses also need to recognize non–infusion-related AEs, particularly in the context of combination therapy, which is typical in the relapsed and refractory setting.

To most effectively implement the use of SC daratumumab, nurses need to be familiar with data from clinical trials while simultaneously demonstrating excellent communication skills, as both are needed in the shared decision-making process. Nurses should be prepared to discuss the benefits and risks of daratumumab in the context of other treatment options. They also need to prepare patients for the experience of SC daratumumab administration—from the constant pressure felt from an SC injection to the possible AEs that may occur. For patients and nurses, a positive experience with SC daratumumab depends on adequate preparation.

References

1. American Cancer Society. Key statistics about multiple myeloma. American Cancer Society website. www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Updated January 8, 2020. Accessed April 9, 2020.
2. National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975- 2015. Surveillance, Epidemiology, and End Results Program website. https://seer.cancer.gov/archive/csr/1975_2015/browse_csr.php?sectionSEL=18&pageSEL=sect_18_table.08. Published 2015. Accessed April 9, 2020.
3. Fonseca R, Abouzaid S, Bonafede M, et al. Trends in overall survival and costs of multiple myeloma, 2000–2014. Leukemia. 2017;31:1915-1921.
4. Dana-Farber Cancer Institute. Multiple myeloma: optimizing quality of life for survivors. Published August 21, 2017. Updated August 22, 2017. https://blog.dana-farber.org/insight/2017/08/multiple-myeloma-optimizing-quality-of-life-for-survivors/. Accessed May 29, 2020.
5. Nielsen LK, Jarden M, Andersen CL, Frederiksen H, Abildgaard N. A systematic review of health-related quality of life in longitudinal studies of myeloma patients. Eur J Haematol. 2017;99:3-17.
6. Durie BGM. Multiple myeloma: concise review of the disease and treatment options. International Myeloma Foundation website. www.myeloma.org/sites/default/files/resource/ConciseReview.pdf. Published 2018. Accessed April 20, 2020.
7. Rajkumar SV, Kyle RA. Progress in myeloma — a monoclonal breakthrough. N Engl J Med. 2016;375:1390-1392.
8. Darzalex [package insert]. Horsham, PA: Janssen Biotech, Inc; 2019.
9. Stewart J. Darzalex approval history. Drugs.com website. www.drugs.com/history/darzalex.html. Updated September 30, 2019. Accessed April 20, 2020.
10. King T, Jagger J, Wood J, et al. Best practice for the administration of daratumumab in multiple myeloma: Australian myeloma nurse expert opinion. Asia Pac J Oncol Nurs. 2018;5:270-284.
11. Barr H, Dempsey J, Waller A, et al. Ninety-minute daratumumab infusion is safe in multiple myeloma. Leukemia. 2018;32:2495-2518.
12. Rifkin R, Singer D, Aguilar KM, Baidoo B, Maiese EM. Daratumumab split first versus single dosing schedule among patients with multiple myeloma treated in a US community oncology setting: a retrospective observational study. Clin Ther. 2019;41:866-881.e7.
13. Mateos M-V, Nahi H, Legiec W, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020;7:e370-e380.
14. Genmab announces U.S. FDA approval of subcutaneous formulation of daratumumab, DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj), for the treatment of patients with multiple myeloma. Genmab A/S. www.globenewswire.com/news-release/2020/05/01/2026290/0/en/Genmab-Announces-U-S-FDA-Approval-of-Subcutaneous-Formulation-of-Daratumumab-DARZALEXFASPRO-daratumumab-and-hyaluronidase-fihj-for-the-Treatment-of-Patientswith-Multiple-Myeloma.html?print=1. Updated May 1, 2020. Accessed May 7, 2020.
15. Darzalex Faspro [package insert]. Horsham, PA: Janssen Biotech, Inc; 2020.
16. Chari A, Nahi H, Mateos M-V, et al. Subcutaneous delivery of daratumumab in patients (pts) with relapsed or refractory multiple myeloma (RRMM): Pavo, an open-label, multicenter, dose escalation phase 1b study. Blood. 2017;130 (suppl 1):838.
17. Usmani SZ, Nahi H, Mateos M-V, et al. Subcutaneous delivery of daratumumab in relapsed or refractory multiple myeloma. Blood. 2019;134:668-677.
18. Janssen submits application to U.S. FDA seeking approval of new Darzalex ® (daratumumab) subcutaneous formulation. News release. Janssen Global Services, LLC. www.janssen.com/janssen-submits-application-us-fda-seeking-approval-new-darzalex-daratumumab-subcutaneous. Updated July 12, 2019. Accessed April 21, 2020.
19. Chari A, Goldschmidt H, San-Miguel J, et al. Subcutaneous (SC) daratumumab (DARA) in combination with standard multiple myeloma (MM) treatment regimens: an open-label, multicenter phase 2 study (PLEIADES). Clin Lymphoma Myeloma Leuk. 2019;19(suppl):e16-e17. Abstract OAB-022.
20. Vidaurri V. Subcutaneous daratumumab with standard therapy in multiple myeloma. 17th International Myeloma Workshop. Oncology Times. November 20, 2019.
21. Martin T. Dr. Martin on subcutaneous administration of daratumumab in multiple myeloma. OncLive website. www.onclive.com/onclive-tv/dr-martin-on-subcutaneous-administration-of-daratumumab-in-multiple-myeloma. Updated January 2, 2020. Accessed April 22, 2020.
22. Orlowski RZ. What are the major side effects associated with daratumumab in combination with bortezomib-dexamethasone, and the best ways to manage them? Managing Myeloma website. www.managingmyeloma.com/knowledge-center/faq-library/946-what-are-the-major-side-effects-associated-with-daratumumab-in-combination-with-bortezomib-dexamethasone-and-the-best-ways-to-manage-them. Updated August 28, 2017. Accessed April 22, 2020.
23. Mateos M-V, Sonneveld P, Hungria V, et al. Daratumumab, bortezomib, and dexamethasone versus bortezomib and dexamethasone in patients with previously treated multiple myeloma: three-year follow-up of CASTOR. Clin Lymphoma Myeloma Leuk. 2019. doi: 10.1016/j.clml.2019.09.623.
24. Kane HL, Halpern MT, Squiers LB, Treiman KA, McCormack LA. Implementing and evaluating shared decision making in oncology practice. CA Cancer J Clin. 2014;64:377-388.
25. Tariman JD, Szubski KL. The evolving role of the nurse during the cancer treatment decision-making process: a literature review. Clin J Oncol Nurs. 2015;19:548-556.