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Once-Weekly vs Twice-Weekly Bortezomib for Newly Diagnosed Multiple Myeloma
abstract
This abstract is available on the publisher's site.
Access this abstract nowInduction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18-70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM.
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Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis
Blood Cancer J 2024 Mar 22;14(1)52, FW Hoff, R Banerjee, AM Khan, G McCaughan, B Wang, X Wang, J Roose, LD Anderson, AJ Cowan, SV Rajkumar, G KaurFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Hoff and colleagues report on a real-world analysis derived from the Flatiron Health database of 2520 patients with myeloma treated with bortezomib between 2017 and 2022. They aimed to better understand the efficacy and safety of weekly versus biweekly administration of bortezomib. The authors document a significant rise in the use of weekly bortezomib from 57.7% in 2017 to 73.1% in 2022. The authors also report a significant decrease in the rate of peripheral neuropathy in patients who received weekly bortezomib (18.5% vs 34.7%) and in the use of medications for the treatment of neuropathy (14.7% vs 29.9%). They found no discernible differences with regard to outcomes.
The authors (correctly) state that peripheral neuropathy was under-reported, as many more patients received medications for the treatment of neuropathy (four times as many) than those with a formal diagnostic code for neuropathy. This is a critical point to understand for future real-world analyses where a specific diagnostic code must be entered by a busy clinician — a person who will feel the completeness of the job by providing symptomatic medication but with no incentive (or need) to add another ICD code. In future studies, the incorporation of natural language processing may be better able to extract information about underlying neuropathy in patients with exposure to bortezomib. Various clinical trials, some of which mandated more detailed documentation of toxicity, show a much higher prevalence of neuropathy.
Clinicians need to be aware of the very high rate of neuropathy associated with bortezomib and the ominous consequences it has on the quality of life of long-term myeloma survivors — many of whom will now live more than 10 years. Importantly, neuropathy needs to be reported for all grades. Even grade 1 is of consequence (enduring symptoms). The CTC criteria specify that grade 2 neuropathy is characterized by “moderate symptoms, limiting instrumental activities of daily living.” In elderly individuals, neuropathy can be associated with a loss of balance and the consequent risk of falls and fractures. Accordingly, all clinical trials should report all grades of neuropathy and whether pain was present. Few, if any, exceptions exist where twice-weekly administration of bortezomib should ever be used. To better serve patients with myeloma, clinicians should not minimize the real risk of bortezomib-induced peripheral neuropathy. Neuropathy is a toxicity that is usually irreversible and without any corrective treatments.
Table. Bortezomib and Neuropathy — Various Clinical Trials
Neuropathy
Grade 3–4
SWOG 0777
Neurological
80%
34
Pain
53%
12
ALCYONE
Dara
28%
1%
Control
34%
4%
ENDURANCE1
VRd arm
53%
8%
VISTA
VMP arm
44%
14%
Pain
36%
9%
E1A05
VRd
35%
13%
VD
28%
16%
Determination
VRd only
73%
-
VRd plus SCT
66%
-
CASSIOPEIA2
Dara-VTd
57%
4%
VTd
52%
4%
PERSEUS
Dara-VRd
54%
4%
VRd
52%
4%
Weekly vs biweekly bortezomib
Weekly
Biweekly
Hoff et al
n = 1522
n = 910
Any neuropathy or medications
35%
0.19
Neuropathy medications
15%
0.3
BOSTON3
32%
0.47
Mateos et al
Matched analyses
32 (4)
47 (14)
Bringhen et al
40%
0.72
Pain
8%
0.13
Persistence
36%
0.34
Better
30%
0.36
Discontinuation due to PN
5%
0.15
Abbreviations: Dara, daratumumab; VRd, bortezomib, lenalidomide, and dexamethasone; VMP, bortezomib, melphalan, and prednisone; SCT, stem-cell transplantation; VTd, bortezomib, thalidomide, and dexamethasone; PN, peripheral neuropathy
1Grade 1 and 2 reports not mandated
2Prior bortezomib in about 70%
3Thalidomide may be part of treatment