From Challenges Spring Opportunities for Progress in Daratumumab-Based Clinical Pathways

An abstract presented at the 63rd Annual American Society of Hematology Annual Meeting and Exposition shows that although daratumumab use in multiple myeloma holds great promise, challenges remain in the use of clinical pathways for treatment direction with the monoclonal antibody—which the investigators say may also present opportunities for change.

Clinical pathways aim not only to improve the quality of health,1 but also to guide evidence-based health care strategies and put into practice guideline recommendations.2 This has proven especially difficult with multiple myeloma (MM) due to the heterogenous nature of the incurable, chronic blood disorder.

“Mapping Myeloma: A Roadmap of Daratumumab Use in Clinical Pathways,” an abstract presented on Monday, December 13, 2021, during the 63rd Annual American Society of Hematology (ASH) Meeting and Exposition in Atlanta, Georgia, explained the results of an investigation into the use of clinical pathways pertaining to daratumumab utilization in first- through fourth-line treatment and beyond.3

Daratumumab is an injectable immunoglobulin G1 kappa (IgG1κ) anti–CD-38 monoclonal antibody used as both monotherapy and combination therapy, with indications for use among several patient groups, including those with a new MM diagnosis who are ineligible for autologous stem cell transplant, those who have received at least 1 prior therapy, and those with relapsed or refractory disease.4

“There is little guidance on treatment selection and sequencing,” the authors from Dana-Farber Cancer Institute (DFCI) wrote. “Clinical pathways have been implemented at different institutions as a decision support tool for the treatment of complex diseases.”

Their August 2019-August 2020 real-world, single-center, retrospective, observational study3 focused on myeloma pathway navigations for daratumumab-based regimens for MM, of which 5 were seen among 45 patients—of the 47 who were on a daratumumab-based treatment course—who received at least 1 treatment dose:

  • Daratumumab/pomalidomide/dexamethasone (45%)
  • Daratumumab/bortezomib/dexamethasone (26%)
  • Daratumumab/dexamethasone (13%)
  • Daratumumab/carfilzomib/lenalidomide/dexamethasone (2%)
  • Daratumumab/pomalidomide/bortezomib (6%)

Charts were reviewed for response rate, overall survival, time to response, duration of response, and time to treatment failure (TTF), as well as concordance between clinical setting and treatment and pathway, with any differences indicating a “discordant navigation.”

Most patients received daratumumab-based regimens as second- or third-line treatment, at 30% and 45%, respectively. Fourth-line and beyond treatment comprised daratumumab-based regimens in 23%. Few patients received such treatments in the first line (2%). Neither overall survival nor duration of response were reached (95% CI, 8.4 months–not reached and 5.8 months–not reached, respectively), although the overall response rate was 62% (range, 47%-76%) and median time to first response, 1 (range, 0.1-7.6) month. Nine percent had a complete response, 24% a very good partial response (PR), 29% a PR, 27% stable disease, and 11% progressive disease.

The shortest TTF was seen in the fourth-line setting and the longest TTF was seen in the first-line setting: 2.5 vs 7.7 months. The median TTF was 3.9 (range, 3.0-7.5) months.

Those who transitioned to subsequent therapy typically either added to their current therapy (26%) or switched to a new regiment altogether (21%), with median time on these subsequent therapies being 3.4 months. Just 6% remained on daratumumab while switching out with new combination agents.

Close to one-third (32% of 47 navigations) of all patients’ records indicated a discordant navigation—despite all receiving treatment “as indicated by the medical chart”—with the reasons for such a designation being line-of-therapy discordance (14.9%), drug selection in treatment plan (6.4%), line-of-therapy and drug-selection discordance (4.3%), decision point discordance (4.3%), and no daratumumab received (2.1%)

Overall, despite the results showing that most study participants received daratumumab in later lines of treatment, TTF was optimal in the second line, besting third- and fourth-line use of daratumumab by 4 and 5.2 months, respectively, the authors noted. In fact, greater benefits were not seen in later-line settings.

“The nuances of myeloma care present a challenge and opportunity,” the authors concluded, “for the development of clinical pathways and guidance in this field.”

References

1. Lawal AK, Rotter T, Kinsman L, et al. What is a clinical pathway? refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review. BMC Med. Published online February 23, 2016. doi:10.1186/s12916-016-0580-z

2. Rotter T, Baatenburg de Jong R, Lacko SE, Ronellenfitsch U, Kinsman L. Clinical pathways as a quality strategy. In: Busse R, KLazinga N, Panteli D, et al, eds. Improving Healthcare Quality in Europe: Characteristics, Effectiveness and Implementation of Different Strategies. European Observatory on Health Systems and Policies; 2019.

3. Hossain S, Leblebjian H, Jackman DM, et al. Mapping myeloma: a roadmap of daratumumab use in clinical pathways. Presented at: 63rd Annual American Society of Hematology Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 4021. Accessed December 13, 2021. https://ash.confex.com/ash/2021/webprogram/Paper149482.html

4. Darzalex Faspro (daratumumab and hyaluronidase-fihj). Prescribing information. Janssen oncology; 2021. Accessed December 13, 2021. https://www.darzalexhcp.com/faspro/indications