Real-World Experience of Weekly Carfilzomib in Combination with Cyclophosphamide and Dexamethasone in Multiple Myeloma Relapsed/Refractory to Bortezomib and Lenalidomide

Cheongin Yang; Changgon Kim; Kunye Kwak; Ka-Won Kang; Yong Park; Byung Soo Kim; Seong Hyun Jeong; Joon Seong Park; Yoon Seok Choi

doi:10.4143/crt.2025.418

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Original Article Hematologic malignancy Real-World Experience of Weekly Carfilzomib in Combination with Cyclophosphamide and Dexamethasone in Multiple Myeloma Relapsed/Refractory to Bortezomib and Lenalidomide: Cheongin Yang¹, Changgon Kim², Kunye Kwak², Ka-Won Kang², Yong Park², Byung Soo Kim², Seong Hyun Jeong¹, Joon Seong Park¹, Yoon Seok Choi^1,2; Cancer Research and Treatment : Official Journal of Korean Cancer Association 2026;58(1):320-328.
DOI: https://doi.org/10.4143/crt.2025.418
Published online: April 25, 2025

¹Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea

²Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea

Correspondence: Joon Seong Park, Department of Hematology-Oncology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Korea
Tel: 82-31-219-5140 E-mail: jspark65@aumc.ac.kr

Co-correspondence: Yoon Seok Choi, Department of Internal Medicine, Korea University College of Medicine, 73 Goryeodae-ro Sungbuk-gu, Seoul 02841, Korea
Tel: 82-2-2199-3816 E-mail: wyfran@korea.ac.kr

• Received: April 17, 2025 • Accepted: April 24, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract

Purpose
This retrospective study evaluated the efficacy and safety of a weekly carfilzomib, cyclophosphamide, and dexamethasone (KCd) regimen in patients with relapsed or refractory multiple myeloma (RRMM) who had been previously treated with both bortezomib- and lenalidomide-containing regimens.
Materials and Methods
We conducted a retrospective analysis of 33 patients with RRMM who received the KCd regimen between March 2020 and February 2024. All patients had prior exposure to both bortezomib and lenalidomide, and the majority (93.9%) were refractory to lenalidomide. Carfilzomib was administered once weekly at 70 mg/m² (after a step-up dose), along with oral cyclophosphamide and dexamethasone. Treatment response was assessed according to the International Myeloma Working Group criteria, and survival outcomes were analyzed.
Results
The overall response rate was 66.7%, including a complete response or better in 15.1% of patients and a very good partial response or better in 42.4%. With a median follow-up of 31.7 months, the median progression-free survival was 13.5 months (95% confidence interval, 11.47 to 15.53), while the median overall survival was not reached. The most common grade ≥ 3 adverse event was neutropenia (15.2%). Non-hematologic grade ≥ 3 toxicities were infrequent and manageable.
Conclusion
The weekly KCd regimen demonstrated encouraging efficacy and tolerability in a heavily pretreated RRMM population. These findings support its use as a feasible treatment option, particularly in patients refractory to lenalidomide.
Key words: Multiple myeloma, Carfilzomib, Cyclophosphamide, Relapsed/refractory, Treatment outcome, Safety profile

Introduction

Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by the proliferation of antibody-producing plasma cells within the bone marrow and is the second most common hematologic malignancy worldwide [1-3]. Over the last two decades, the therapeutic landscape of MM has dramatically evolved largely due to the development and clinical integration of novel agents such as proteasome inhibitors, immunomodulatory drugs (IMiDs), and monoclonal antibodies [4,5]. Among these, proteasome inhibitors represent a fundamental component of various anti-myeloma treatment protocols [6,7]. Carfilzomib, a highly potent and selective irreversible inhibitor of the proteasome, has shown substantial clinical efficacy when used in combination with other therapeutic agents for the treatment of MM, especially in the relapsed or refractory setting [8-10]. Notably, its combination with dexamethasone or IMiDs has demonstrated improved survival outcomes in randomized clinical trials [11-13].

Despite these therapeutic advances, clinical outcomes remain particularly poor for patients who are refractory to both bortezomib- and lenalidomide-based regimens [14]. These patients typically have limited treatment options, exhibit low response rates to salvage therapies, and often experience rapid disease progression, thereby representing a population with a critical unmet need [15]. In this context, carfilzomib-based combination regimens have garnered increasing interest as potential therapeutic strategies [10]. The combination of carfilzomib with cyclophosphamide and dexamethasone (KCd) has emerged as a promising triplet regimen. Cyclophosphamide, an alkylating agent with both cytotoxic and immunomodulatory properties, is widely available, cost-effective, and generally well-tolerated, making it a practical partner in combination therapies—especial in patients who are not candidates for IMiD-based treatment due to prior refractoriness and intolerance.

The combination of carfilzomib with cyclophosphamide in the frontline setting has been investigated in both transplant-ineligible and transplant-eligible patients with newly diagnosed MM, consistently demonstrating favorable efficacy and a manageable safety profile [16-19]. Moreover, emerging data suggest that this regimen may also provide clinical benefit in relapsed or refractory disease, particularly among patients with prior exposure to bortezomib and/or lenalidomide [20-23]. Of note, weekly administration of carfilzomib, an alternative to the conventional twice-weekly schedule, has shown comparable efficacy while improving convenience and tolerability, potentially enhancing treatment adherence without compromising outcomes [20,23-25].

Although the KCd regimen has shown encouraging results in the treatment of relapsed or refractory MM (RRMM), real-world evidence regarding its efficacy and safety remains limited. Importantly, no studies to date have evaluated this regimen specifically in Asian populations, highlighting the need for ethnicity-specific clinical data. This study, therefore, aims to evaluate the clinical outcomes of weekly KCd therapy in patients with RRMM who have been previously treated with both bortezomib and lenalidomide, thus generating real-world evidence to support the feasibility and effectiveness of this regimen in routine clinical settings.

Materials and Methods

1. Patients selection

This retrospective analysis included 33 consecutive patients with RRMM who received the KCd regimen at Ajou University Medical Center between March 2020 and February 2024. All patients had previously relapsed after or were refractory to both bortezomib-containing and lenalidomide-containing regimens. Eligible patients were required to have measurable disease as defined by the International Myeloma Working Group (IMWG) criteria [26], an Eastern Cooperative Oncology Group performance status of 0-1, and adequate cardiac function as assessed by echocardiography prior to the initiation of therapy.

2. Treatment protocol

Carfilzomib was administered as a 30-minute intravenous infusion at a dose of 20 mg/m² on day 1 of cycle 1, and 70 mg/m² on days 8 and 15 of cycle 1, and subsequently on days 1, 8, and 15 of each 28-day cycle. Cyclophosphamide was administered orally at a dose of 300 mg/m² (capped at 500 mg) on days 1, 8, and 15 of each cycle. Dexamethasone was administered either orally or intravenously at 40 mg on days 1, 8, 15, and 22 (reduced to 20 mg for patients aged > 75 years). Following the completion of 13 treatment cycles, treatment was administered every other week and cyclophosphamide was discontinued. Thereafter, the dosing of dexamethasone was determined at the discretion of the treating physician. The strategies applied to manage treatment-emergent adverse events in patients included in this study are detailed in S1 Table. For carfilzomib, dose reductions were permitted from the initial dose to 56 mg/m² and subsequently to 45 mg/m². For cyclophosphamide, dose reductions were allowed in 100 mg decrements from the starting dose. Treatment continued until disease progression, the occurrence of unacceptable toxicity, or physician decision to discontinue therapy.

3. Efficacy and safety assessments

The primary objective of this study was to evaluate the efficacy and safety of the KCd regimen in patients with RRMM previously treated with both bortezomib- and lenalidomide-containing therapies. Efficacy and safety assessments were performed at the end of each treatment cycle. Clinical response was evaluated in accordance with the IMWG response criteria [25]. Treatment-emergent adverse events were documented and graded using the National Cancer Institute’s Common Terminology Criteria for Adverse Events, ver. 4.3.

4. Statistical methods

Progression-free survival (PFS) was defined as the time from the first administration of KCd to the date of disease progression or death from any cause. Overall survival (OS) was defined as the time from the first administration of KCd to death from any cause. Survival curves were estimated using the Kaplan-Meier method and differences in survival between subgroups were assessed using the log-rank test. To explore potential prognostic factors associated with survival, univariate Cox proportional hazards regression analyses were conducted using baseline clinical variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for each factor. Additionally, multivariable Cox regression models were constructed to assess the independent impact of these variables on survival outcomes. Baseline demographic and clinical characteristics, treatment responses, and safety outcomes were summarized using descriptive statistics. All statistical analyses were performed using IBM SPSS ver. 25.0 (IBM Corp.) and a two-sided p-value < 0.05 was considered statistically significant.

Results

1. Demographics and characteristics

Between March 2020 and February 2024, a total of 33 patients were treated with the KCd regimen and analyzed retrospectively. Patient demographics and baseline clinical characteristics are summarized in Table 1. The median age of participants was 64 years, with an age range from 46 to 78 years. The predominant paraprotein isotype was IgG (57.6%), followed by light chain (27.3%) and IgA (15.1%). According to the revised International Staging System (R-ISS), 45.5% of patients were classified as stage III, 42.4% as stage II, and 12.1% as stage I. High-risk cytogenetic abnormalities, including t(4;14), t(14;16), and del(17p), were observed in 33.3% of patients. Extramedullary disease was identified in 6.1% of cases.

All patients had been previously treated with both bortezomib- and lenalidomide-containing regimens and were considered relapsed or refractory to at least one of them. Notably, 93.9% of patients were refractory to lenalidomide, while the remaining two non-refractory patients had previously discontinued lenalidomide-containing regimens due to treatment-related adverse events rather than disease progression. These patients subsequently received the current regimen upon progression. A substantial proportion (60.6%) had undergone prior autologous stem cell transplantation (ASCT). In terms of treatment history, 27.3% had received one prior line of therapy, 48.5% had received two lines, and 24.2% had received three.

2. Treatment response

As shown in Table 2, the overall response rate (ORR) to the KCd regimen was 66.7%. A stringent complete response (sCR) was achieved in two patients (6.1%), complete response (CR) in three (9.1%), very good partial response (VGPR) in nine (27.3%), and partial response (PR) in eight (24.2%). The proportion of patients who achieved VGPR or better was 42.4%, and CR or better was noted in 15.1% of cases. These findings suggest that KCd therapy provides meaningful clinical benefit in RRMM population, particularly in the context of high lenalidomide-refractoriness. Among patients with high-risk cytogenetic abnormalities (n=11), the ORR was 63.6%, with one sCR, one CR, three VGPR, and two PRs observed. The proportion of patients achieving VGPR or better was 45.5%. These findings support that KCd can offer clinically significant responses even in patients with aggressive disease biology.

3. Survival analysis

At the time of data cutoff, with a median follow-up duration of 31.7 months, 26 patients (78.8%) experienced disease progression or death. The median PFS was 13.5 months (95% CI, 11.47 to 15.53) (Fig. 1A). The median OS had not been reached at the time of data analysis (Fig. 1B), with several patients continuing treatment or follow-up beyond 30 months. Survival outcomes were further examined through subgroup analyses based on key baseline characteristics. The full set of Kaplan-Meier curves for PFS and OS stratified by each variable is presented in Fig. 2 and S2 Fig., respectively. Patients with age < 65 years demonstrated significantly longer PFS compared to those with age ≥ 65 years. Similarly, patients who had received ASCT showed significantly longer PFS compared to those without prior ASCT.

In univariate Cox regression analysis, as shown in Fig. 3, prior ASCT was significantly associated with improved survival outcomes. Patients with prior ASCT demonstrated longer PFS (HR, 0.44; 95% CI, 0.20 to 0.96; p=0.040) and OS (HR, 0.28; 95% CI, 0.08 to 0.97; p=0.044) compared to those without ASCT history. Age ≥ 65 years was also associated with inferior OS (HR, 3.86; 95% CI, 1.02 to 14.65; p=0.047), while a similar trend was observed for PFS (HR, 2.15; 95% CI, 0.98 to 4.70; p=0.056). No significant associations were found for R-ISS stage or high-risk cytogenetic status in univariate models. Multivariable analysis did not identify any baseline clinical variables as statistically significant independent predictors of survival.

4. Safety and tolerability

Treatment-emergent adverse events were generally manageable (Table 3). The most common hematologic toxicities of grade 3 or higher were neutropenia, observed in 15.2% of patients. Grade ≥ 3 non-hematologic grade adverse events included pneumonia (6.1%), urinary tract infection (3.0%), diarrhea (3.0%), and fatigue (6.1%). No grade ≥ 3 cardiovascular events were observed during the study period. Frequent adverse events of any grade included fatigue (30.3%), upper respiratory tract infection (21.2%), dyspnea (15.2%), and diarrhea (15.2%).

No treatment-related mortality occurred during the study period, and most adverse events were manageable with standard supportive care. Dose modifications and treatment delays were primarily implemented in response to hematologic toxicities. Specifically, eight patients (24.2%) required dose reduction, and 12 patients (36.4%) experienced temporary interruptions due to toxicity. Among patients who required dose reductions, carfilzomib and cyclophosphamide were simultaneously dose-reduced as part of the toxicity management strategy. No permanent discontinuation of carfilzomib due to cardiovascular events was observed. Weekly administration of carfilzomib was generally well tolerated and enabled sustained drug delivery in an outpatient setting without compromising safety.

Discussion

In this retrospective study, we evaluated the efficacy and safety of a weekly KCd regimen—carfilzomib, cyclophosphamide, and dexamethasone—in patients with RRMM who had been previously exposed to both bortezomib and lenalidomide. Our findings demonstrate that KCd provides a clinically meaningful benefit in this heavily pretreated population, with an ORR of 66.7% and a median PFS of 13.5 months. Notably, the regimen was well tolerated, with manageable adverse events and no treatment-related mortality observed.

While the absence of a comparator arm limits the interpretation of efficacy outcomes in this single-arm retrospective study, we attempted to contextualize our findings through indirect comparisons with previously reported studies. The clinical efficacy observed in our study is consistent with previous reports evaluating KCd in relapsed/refractory settings (Table 4). This combination could be a viable option for patients resistant to IMiDs, where treatment choices are limited [6,15]. The high proportion of patients achieving VGPR or better in our study (42.4%) further supports the regimen’s potency in the context of IMiD-refractory disease. The observed median PFS of 13.5 months compares favorably to other triplet regimens used in the relapsed/refractory setting, particularly given the inclusion of patients with high-risk cytogenetics (33.3%) and a substantial number of patients with two or more prior lines of therapy. Although the median OS was not reached at the time of analysis, the survival curve suggests a durable benefit for a subset of patients, warranting longer follow-up and further investigation. Furthermore, when compared to alternative regimens used in lenalidomide-refractory MM—such as the pomalidomide, cyclophosphamide, and dexamethasone (PCD) regimen—our results suggest a more favorable efficacy profile. Previously reported median PFS values for PCD in similar populations have typically ranged from 4 to 9 months [27-29], whereas our study achieved a median PFS of 13.5 months. Although such cross-study comparisons should be interpreted with caution due to variations in study design and patient characteristics, our findings reinforce the potential of weekly KCd as an effective and feasible treatment option in heavily pretreated and lenalidomide-refractory patients.

One of the strengths of our study is the use of a weekly carfilzomib dosing schedule, which has been shown in prior trials to provide comparable efficacy to twice-weekly administration, with improved convenience and potentially better tolerability. In our cohort, this approach enabled consistent drug delivery in the outpatient setting with an acceptable safety profile. The most common grade ≥ 3 hematologic toxicity was neutropenia (15.2%), while non-hematologic toxicities were infrequent and generally manageable with supportive care. Despite concerns regarding the cardiovascular toxicity associated with carfilzomib, no clinically significant cardiac adverse events were observed in the present study [30].

Despite these encouraging findings, several limitations should be considered. First, the retrospective design and single-center nature of the study introduce potential selection bias and limit generalizability. Second, the relatively small sample size reduces statistical power and precludes definitive subgroup analyses, particularly with respect to cytogenetic risk or prior treatment exposures. Due to the limited sample size and the number of events, model stability could not be fully ensured in the multivariable Cox regression analysis and most variables did not retain statistical significance. Third, although the study population was uniformly treated with the KCd regimen, variations in dexamethasone dosing after 13 cycles may have influenced long-term outcomes.

In the present study, we provide important real-world evidence supporting the use of KCd in RRMM, particularly in patients who have exhausted both bortezomib- and lenalidomide-based therapies. Given the favorable response rates, manageable toxicity, and practical feasibility of weekly carfilzomib administration, the KCd regimen represents a valuable option in the treatment landscape of MM. Prospective studies in larger, more diverse populations are warranted to confirm these findings and to further refine the role of this combination in the evolving treatment paradigm.

Electronic Supplementary Material

Supplementary materials are available at Cancer Research and Treatment website (https://www.e-crt.org).

crt-2025-418_S1_Table.pdf

crt-2025-418_S2_Fig.pdf

NOTES

Ethical Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Declaration of Helsinki or comparable ethical standards. Waiving any informed consent was approved by the institutional review boards of Ajou University Hospital (AJOUIRB-OBS-2021-484).

Author Contributions

Conceived and designed the analysis: Park JS, Choi YS.

Collected the data: Yang C, Jeong SH, Park JS, Choi YS.

Contributed data or analysis tools: Yang C, Kwak K, Jeong SH, Park JS, Choi YS.

Performed the analysis: Yang C, Kim C, Kwak K, Kang KW, Park Y, Kim BS, Jeong SH.

Wrote the paper: Yang C, Park JS, Choi YS.

Conflicts of Interest

Conflict of interest relevant to this article was not reported.

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (RS-2022-NR070625 to Y.S.C.).

Fig. 1.

Survival outcomes of the study treatment in patients with relapsed/refractory multiple myeloma. (A) The Kaplan-Meier curves of progression-free survival (PFS) in the study population (n=33). (B) The Kaplan-Meier curves of overall survival (OS) in the study population. CI, confidence interval.

Fig. 2.

Subgroup analysis of progression-free survival (PFS) according to the pre-treatment clinical and cytogenetic parameters in the study group. PFS was compared across clinical subgroups defined by age (< 65 vs. ≥ 65 years) (A), revised International Staging System (R-ISS) stage (I, II, III) (B), cytogenetic risk status (standard- vs. high-risk) (C), prior autologous stem cell transplantation (ASCT) (D), and number of prior lines of therapy (1, 2, or 3) (E). Median PFS and p-values were calculated using the log-rank test. CI, confidence interval.

Fig. 3.

Univariate Cox proportional hazards analysis of survival outcomes. Forest plot showing hazard ratios and 95% confidence intervals for progression-free survival (A) and overall survival (B) according to baseline clinical characteristics. The number of patients in each subgroup is indicated. Error bars represent 95% confidence intervals. p-values are based on Wald tests. ASCT, autologous stem cell transplantation; R-ISS, revised international staging system.

Table 1.

Baseline characteristics of patients included in the current study

Characteristic	No. (%) (n=33)
Age (yr), median (range)	64 (46-78)
Sex
Male	15 (45.5)
Female	18 (54.5)
Isotype of paraprotein
IgG	19 (57.6)
IgA	5 (15.1)
Light chain	9 (27.3)
R-ISS stage
I	4 (12.1)
II	14 (42.4)
III	15 (45.5)
Cytogenetics
Standard-risk	22 (66.7)
High-risk	11 (33.3)
Extramedullary disease	2 (6.1)
LV ejection fraction (%), median (range)	64 (56-69)
Number of prior lines of therapy
1 prior line	9 (27.3)
2 prior lines	16 (48.5)
3 prior lines	8 (24.2)
Prior autologous stem cell transplantation	20 (60.6)
Prior anti-myeloma therapy
Exposure to bortezomib	33 (100)
Exposure to thalidomide	14 (42.4)
Exposure to lenalidomide	33 (100)
Exposure to daratumumab	1 (3.0)
Refractoriness to bortezomib	5 (15.1)
Refractoriness to lenalidomide	31 (93.9)

High-risk cytogenetics include t(4;14), t(14;16) and 17p–. R-ISS, revised International Staging System.

Table 2.

Response rate to KCd regimen

Efficacy	No. (%) (n=33)
Stringent complete response	2 (6.1)
Complete response	3 (9.1)
Very good partial response	9 (27.3)
Partial response	8 (24.2)
Minimal response	3 (9.1)
Stable disease	5 (15.1)
Progressive disease	3 (9.1)
Overall response	22 (66.7)
Very good response or better	14 (42.4)
Complete response or better	5 (15.1)

Values are presented as number (%). Tumor response was assessed according to International Myeloma Working Group criteria. KCd, carfilzomib, cyclophosphamide, and dexamethasone.

Table 3.

Treatment-emergent adverse events

Adverse event	Grade 1-2	Grade 3-4
Hematologic events
Thrombocytopenia	4 (12.1)	2 (6.1)
Neutropenia	5 (15.2)	5 (15.2)
Anemia	7 (21.2)	2 (6.1)
Non-hematologic events
Cardiovascular events
Hypertension	3 (9.1)	0
Atrial fibrillation	1 (3.0)	0
Dyspnea	5 (15.2)	0
Infection
Pneumonia	1 (3.0)	2 (6.1)
Upper respiratory tract infection	7 (21.2)	0
Urinary tract infection	0	1 (3.0)
Rash	2 (6.1)	0
Diarrhea	5 (15.2)	1 (3.0)
Fatigue	10 (30.3)	2 (6.1)

Values are presented as number (%).

Table 4.

Studies of KCd therapy in RRMM

Study	Study design	No. of patients	Age (yr), median	Prior lines of therapy	Treatment protocol	ORR (%)	Median PFS (mo)
Venner et al. [20]	Prospective	75	66	1 in 39%	K: 70 mg/m² on D1/8/15	85.3	17.2
				2 in 44%	C: 300 mg/m² on D1/8/15/22
				3 in 17%	d: 40 mg on D1/8/15/22
Yong et al. [21]	Prospective	201	67	1 in 100%	K: 36 mg/m² on D1/2/8/9/15/16	84.0	11.7
					C: 500 mg on D1/8/15
					d: 40 mg on D1/8/15/22
Pennipede et al. [22]	Retrospective	23	54	Median 6 (range 3-10)	K: 36 mg/m² on D1/2/8/9/15/16	52.2	4.0
					C: 500 mg on D1/8/15/22
					d: 40 mg on D1/8/15/22
Puertas et al. [23]	Prospective	97	70	1 in 67.0%	K: 70 mg/m² on D1/8/15	72.4	19.1
				2 in 23.7%	C: 300 mg/m² on D1/8/15
				3 in 9.3%	d: 40 mg on D1/8/15/22
Current study	Retrospective	33	64	1 in 27%	K: 70 mg/m² on D1/8/15	66.7	13.5
				2 in 49%	C: 300 mg/m² on D1/8/15
				3 in 24%	d: 40 mg on D1/8/15/22

Patients received carfilzomib at a dose of 20 mg/m² on day 1 of cycle 1 in all studies listed. KCd, carfilzomib, cyclophosphamide and dexamethasone; ORR, overall response rate; PFS, progression-free survival; RRMM, relapsed or refractory multiple myeloma.

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Real-World Experience of Weekly Carfilzomib in Combination with Cyclophosphamide and Dexamethasone in Multiple Myeloma Relapsed/Refractory to Bortezomib and Lenalidomide

Cancer Res Treat. 2026;58(1):320-328. Published online April 25, 2025

DOI: https://doi.org/10.4143/crt.2025.418

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Abstract
Introduction
Materials and Methods
Results
Discussion
Electronic Supplementary Material
NOTES
REFERENCES

Real-World Experience of Weekly Carfilzomib in Combination with Cyclophosphamide and Dexamethasone in Multiple Myeloma Relapsed/Refractory to Bortezomib and Lenalidomide

Fig. 1. Survival outcomes of the study treatment in patients with relapsed/refractory multiple myeloma. (A) The Kaplan-Meier curves of progression-free survival (PFS) in the study population (n=33). (B) The Kaplan-Meier curves of overall survival (OS) in the study population. CI, confidence interval.

Fig. 2. Subgroup analysis of progression-free survival (PFS) according to the pre-treatment clinical and cytogenetic parameters in the study group. PFS was compared across clinical subgroups defined by age (< 65 vs. ≥ 65 years) (A), revised International Staging System (R-ISS) stage (I, II, III) (B), cytogenetic risk status (standard- vs. high-risk) (C), prior autologous stem cell transplantation (ASCT) (D), and number of prior lines of therapy (1, 2, or 3) (E). Median PFS and p-values were calculated using the log-rank test. CI, confidence interval.

Fig. 3. Univariate Cox proportional hazards analysis of survival outcomes. Forest plot showing hazard ratios and 95% confidence intervals for progression-free survival (A) and overall survival (B) according to baseline clinical characteristics. The number of patients in each subgroup is indicated. Error bars represent 95% confidence intervals. p-values are based on Wald tests. ASCT, autologous stem cell transplantation; R-ISS, revised international staging system.

Fig. 1.

Fig. 2.

Fig. 3.

Real-World Experience of Weekly Carfilzomib in Combination with Cyclophosphamide and Dexamethasone in Multiple Myeloma Relapsed/Refractory to Bortezomib and Lenalidomide

Characteristic	No. (%) (n=33)
Age (yr), median (range)	64 (46-78)
Sex
Male	15 (45.5)
Female	18 (54.5)
Isotype of paraprotein
IgG	19 (57.6)
IgA	5 (15.1)
Light chain	9 (27.3)
R-ISS stage
I	4 (12.1)
II	14 (42.4)
III	15 (45.5)
Cytogenetics
Standard-risk	22 (66.7)
High-risk	11 (33.3)
Extramedullary disease	2 (6.1)
LV ejection fraction (%), median (range)	64 (56-69)
Number of prior lines of therapy
1 prior line	9 (27.3)
2 prior lines	16 (48.5)
3 prior lines	8 (24.2)
Prior autologous stem cell transplantation	20 (60.6)
Prior anti-myeloma therapy
Exposure to bortezomib	33 (100)
Exposure to thalidomide	14 (42.4)
Exposure to lenalidomide	33 (100)
Exposure to daratumumab	1 (3.0)
Refractoriness to bortezomib	5 (15.1)
Refractoriness to lenalidomide	31 (93.9)

Efficacy	No. (%) (n=33)
Stringent complete response	2 (6.1)
Complete response	3 (9.1)
Very good partial response	9 (27.3)
Partial response	8 (24.2)
Minimal response	3 (9.1)
Stable disease	5 (15.1)
Progressive disease	3 (9.1)
Overall response	22 (66.7)
Very good response or better	14 (42.4)
Complete response or better	5 (15.1)

Adverse event	Grade 1-2	Grade 3-4
Hematologic events
Thrombocytopenia	4 (12.1)	2 (6.1)
Neutropenia	5 (15.2)	5 (15.2)
Anemia	7 (21.2)	2 (6.1)
Non-hematologic events
Cardiovascular events
Hypertension	3 (9.1)	0
Atrial fibrillation	1 (3.0)	0
Dyspnea	5 (15.2)	0
Infection
Pneumonia	1 (3.0)	2 (6.1)
Upper respiratory tract infection	7 (21.2)	0
Urinary tract infection	0	1 (3.0)
Rash	2 (6.1)	0
Diarrhea	5 (15.2)	1 (3.0)
Fatigue	10 (30.3)	2 (6.1)

Study	Study design	No. of patients	Age (yr), median	Prior lines of therapy	Treatment protocol	ORR (%)	Median PFS (mo)
Venner et al. [20]	Prospective	75	66	1 in 39%	K: 70 mg/m² on D1/8/15	85.3	17.2
				2 in 44%	C: 300 mg/m² on D1/8/15/22
				3 in 17%	d: 40 mg on D1/8/15/22
Yong et al. [21]	Prospective	201	67	1 in 100%	K: 36 mg/m² on D1/2/8/9/15/16	84.0	11.7
					C: 500 mg on D1/8/15
					d: 40 mg on D1/8/15/22
Pennipede et al. [22]	Retrospective	23	54	Median 6 (range 3-10)	K: 36 mg/m² on D1/2/8/9/15/16	52.2	4.0
					C: 500 mg on D1/8/15/22
					d: 40 mg on D1/8/15/22
Puertas et al. [23]	Prospective	97	70	1 in 67.0%	K: 70 mg/m² on D1/8/15	72.4	19.1
				2 in 23.7%	C: 300 mg/m² on D1/8/15
				3 in 9.3%	d: 40 mg on D1/8/15/22
Current study	Retrospective	33	64	1 in 27%	K: 70 mg/m² on D1/8/15	66.7	13.5
				2 in 49%	C: 300 mg/m² on D1/8/15
				3 in 24%	d: 40 mg on D1/8/15/22

Table 1. Baseline characteristics of patients included in the current study

High-risk cytogenetics include t(4;14), t(14;16) and 17p–. R-ISS, revised International Staging System.

Table 2. Response rate to KCd regimen

Values are presented as number (%). Tumor response was assessed according to International Myeloma Working Group criteria. KCd, carfilzomib, cyclophosphamide, and dexamethasone.

Table 3. Treatment-emergent adverse events

Values are presented as number (%).

Table 4. Studies of KCd therapy in RRMM