The
n e w e ng l a n d j o u r na l
1. Sundt TM. Surgery for ischemic mitral regurgitation.
N Engl J Med 2014;371:2228-29. 2. Kron IL, Hung J, Overbey JR, et al. Predicting recurrent mitral regurgitation after mitral valve repair for severe ischemic mitral regurgitation. J Thorac Cardiovasc Surg 2014 November 6 (Epub ahead of print). 3. Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33:2451-96.
of
m e dic i n e
4. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC
guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63(22):e57-e185. 5. Grayburn PA, Carabello B, Hung J, et al. Defining “severe” secondary mitral regurgitation: emphasizing an integrated approach. J Am Coll Cardiol 2014;64:2792-801. DOI: 10.1056/NEJMc1503128
Treatment of Relapsed Multiple Myeloma To the Editor: In the study by Stewart et al. (Jan. 8 issue),1 the improved responses among patients receiving carfilzomib in addition to len alidomide and dexamethasone were associated with a significant improvement in quality of life. Although the hazard ratio for death was also decreased, such a result is difficult to evaluate in the absence of information on treatment that was administered after disease progression in the control group. What percentage of the control patients received carfilzomib after disease progression? In addition, since only 20% of patients were previously treated with lenalidomide, it is not clear what effect the results of this study should have for today’s patients who have generally received lenalidomide for induction therapy, maintenance therapy, or both and presumably have resistance to lenalidomide at the time of disease progression. Although it seems self-evident that better responses are associated with improved survival, is that still true when patients have received more drugs (which could be used later) to achieve the better response? As an example, the use of highdose therapy and autologous bone marrow transplantation as part of induction therapy is consistently associated with an improved response, but studies have not shown a survival advantage for early versus late transplantation. Dennis L. Cooper, M.D.
The authors reply: Cooper raises important questions that were not directly addressed by our study. Only 2% of patients in our study received carfilzomib at the time of relapse, whereas bortezomib was administered to 26% of the patients in the control group versus 13% of those in the carfilzomib group. Although the survival results are trending in favor of the carfilzomib group, the data are immature and may be confounded by the many salvage therapies now available. We agree with Cooper that depth of response is a useful surrogate for survival and believe that it is unlikely that an equivalent rate of complete response (31.8%) would be seen with the use of sequential therapy approaches.1 Although only 20% of our patients received previous lenalidomide, 58% received an immune modulator; a subgroup analysis confirmed an advantage in progressionfree survival among patients who had received previous lenalidomide or who had resistance to any immune modulator. In the presence of lenalidomide resistance, carfilzomib has been successfully combined with pomalidomide.2 We believe that our findings support the value of combination chemotherapy over a sequential approach to drug delivery among patients with relapsed myeloma.
140 Patten Rd. North Haven, CT [email protected] No potential conflict of interest relevant to this letter was reported.
Scottsdale, AZ [email protected]
1. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzo-
Turin, Italy
DOI: 10.1056/NEJMc1501348
Since publication of their article, Dr. Stewart reports receiving consulting fees from Novartis. No further potential conflict of interest relevant to this letter was reported.
mib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015;372:142-52.
1774
A. Keith Stewart, M.B., Ch.B. Mayo Clinic
Antonio Palumbo, M.D. University of Turin
n engl j med 372;18 nejm.org april 30, 2015
The New England Journal of Medicine Downloaded from nejm.org on May 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
correspondence 1. Lonial S, Anderson KC. Association of response endpoints
with survival outcomes in multiple myeloma. Leukemia 2014; 28:258-68. 2. Shah JJ, Stadtmauer EA, Abonour R, et al. Phase I/II dose expansion of a multi-center trial of carfilzomib and pomalido-
mide with dexamethasone (Car-Pom-d) in patients with relapsed/refractory multiple myeloma. Blood 2013;122:Suppl:690. abstract. DOI: 10.1056/NEJMc1501348
Acute Hydrophilic-Polymer Nephropathy and Acute Renal Failure To the Editor: Hydrophilic coatings are used on intravascular devices to facilitate manipulation and to minimize complications such as vasospasm during a procedure and thrombosis after a procedure.1,2 We report a case of vascular intervention associated with acute renal failure in a 42-year-old woman. In 2009, the patient underwent renal trans-
plantation in which the renal artery was implanted into right external iliac artery. Between January and June 2013, her serum creatinine level increased progressively over a 5-month period, from a baseline value of 1.0 mg per deciliter to 2.2 mg per deciliter (normal range, 0.5 to 1.2 mg per deciliter) (Fig. S1 in the Supplementary Appendix, available with the full text of this letter
A
B
C
D
Figure 1. Kidney-Biopsy Results. A percutaneous kidney biopsy revealed intraarteriolar foreign-body emboli (arrows), with associated ischemic collapse of the downstream glomerulus. The findings are seen with periodic acid–Schiff stain and hematoxylin and eosin stain (Panel A) and periodic acid–Schiff stain and methenamine silver stain (Panel B). Foreign-body emboli in interlobular arteries are shown with the use of periodic acid–Schiff stain and hematoxylin and eosin stain (Panel C) and von Kossa’s stain and Masson’s trichrome stain (Panel D).
n engl j med 372;18
nejm.org
april 30, 2015
The New England Journal of Medicine Downloaded from nejm.org on May 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
1775
n e w e ng l a n d j o u r na l
1. Sundt TM. Surgery for ischemic mitral regurgitation.
N Engl J Med 2014;371:2228-29. 2. Kron IL, Hung J, Overbey JR, et al. Predicting recurrent mitral regurgitation after mitral valve repair for severe ischemic mitral regurgitation. J Thorac Cardiovasc Surg 2014 November 6 (Epub ahead of print). 3. Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33:2451-96.
of
m e dic i n e
4. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC
guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63(22):e57-e185. 5. Grayburn PA, Carabello B, Hung J, et al. Defining “severe” secondary mitral regurgitation: emphasizing an integrated approach. J Am Coll Cardiol 2014;64:2792-801. DOI: 10.1056/NEJMc1503128
Treatment of Relapsed Multiple Myeloma To the Editor: In the study by Stewart et al. (Jan. 8 issue),1 the improved responses among patients receiving carfilzomib in addition to len alidomide and dexamethasone were associated with a significant improvement in quality of life. Although the hazard ratio for death was also decreased, such a result is difficult to evaluate in the absence of information on treatment that was administered after disease progression in the control group. What percentage of the control patients received carfilzomib after disease progression? In addition, since only 20% of patients were previously treated with lenalidomide, it is not clear what effect the results of this study should have for today’s patients who have generally received lenalidomide for induction therapy, maintenance therapy, or both and presumably have resistance to lenalidomide at the time of disease progression. Although it seems self-evident that better responses are associated with improved survival, is that still true when patients have received more drugs (which could be used later) to achieve the better response? As an example, the use of highdose therapy and autologous bone marrow transplantation as part of induction therapy is consistently associated with an improved response, but studies have not shown a survival advantage for early versus late transplantation. Dennis L. Cooper, M.D.
The authors reply: Cooper raises important questions that were not directly addressed by our study. Only 2% of patients in our study received carfilzomib at the time of relapse, whereas bortezomib was administered to 26% of the patients in the control group versus 13% of those in the carfilzomib group. Although the survival results are trending in favor of the carfilzomib group, the data are immature and may be confounded by the many salvage therapies now available. We agree with Cooper that depth of response is a useful surrogate for survival and believe that it is unlikely that an equivalent rate of complete response (31.8%) would be seen with the use of sequential therapy approaches.1 Although only 20% of our patients received previous lenalidomide, 58% received an immune modulator; a subgroup analysis confirmed an advantage in progressionfree survival among patients who had received previous lenalidomide or who had resistance to any immune modulator. In the presence of lenalidomide resistance, carfilzomib has been successfully combined with pomalidomide.2 We believe that our findings support the value of combination chemotherapy over a sequential approach to drug delivery among patients with relapsed myeloma.
140 Patten Rd. North Haven, CT [email protected] No potential conflict of interest relevant to this letter was reported.
Scottsdale, AZ [email protected]
1. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzo-
Turin, Italy
DOI: 10.1056/NEJMc1501348
Since publication of their article, Dr. Stewart reports receiving consulting fees from Novartis. No further potential conflict of interest relevant to this letter was reported.
mib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015;372:142-52.
1774
A. Keith Stewart, M.B., Ch.B. Mayo Clinic
Antonio Palumbo, M.D. University of Turin
n engl j med 372;18 nejm.org april 30, 2015
The New England Journal of Medicine Downloaded from nejm.org on May 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
correspondence 1. Lonial S, Anderson KC. Association of response endpoints
with survival outcomes in multiple myeloma. Leukemia 2014; 28:258-68. 2. Shah JJ, Stadtmauer EA, Abonour R, et al. Phase I/II dose expansion of a multi-center trial of carfilzomib and pomalido-
mide with dexamethasone (Car-Pom-d) in patients with relapsed/refractory multiple myeloma. Blood 2013;122:Suppl:690. abstract. DOI: 10.1056/NEJMc1501348
Acute Hydrophilic-Polymer Nephropathy and Acute Renal Failure To the Editor: Hydrophilic coatings are used on intravascular devices to facilitate manipulation and to minimize complications such as vasospasm during a procedure and thrombosis after a procedure.1,2 We report a case of vascular intervention associated with acute renal failure in a 42-year-old woman. In 2009, the patient underwent renal trans-
plantation in which the renal artery was implanted into right external iliac artery. Between January and June 2013, her serum creatinine level increased progressively over a 5-month period, from a baseline value of 1.0 mg per deciliter to 2.2 mg per deciliter (normal range, 0.5 to 1.2 mg per deciliter) (Fig. S1 in the Supplementary Appendix, available with the full text of this letter
A
B
C
D
Figure 1. Kidney-Biopsy Results. A percutaneous kidney biopsy revealed intraarteriolar foreign-body emboli (arrows), with associated ischemic collapse of the downstream glomerulus. The findings are seen with periodic acid–Schiff stain and hematoxylin and eosin stain (Panel A) and periodic acid–Schiff stain and methenamine silver stain (Panel B). Foreign-body emboli in interlobular arteries are shown with the use of periodic acid–Schiff stain and hematoxylin and eosin stain (Panel C) and von Kossa’s stain and Masson’s trichrome stain (Panel D).
n engl j med 372;18
nejm.org
april 30, 2015
The New England Journal of Medicine Downloaded from nejm.org on May 12, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
1775
