Medical Device Reports of Breast Implant-Associated Anaplastic Large Cell Lymphoma
As of January 5, 2020 , the Food and Drug Administration (FDA) has received a total of 733 US and global medical device reports (MDRs) of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). This total includes all breast implant related MDRs the FDA received with any mention of "ALCL" or other spelling variations (for example, "anaplastic lymphoma," or "anaplastic") in the narrative text. In the data presented, BIA-ALCL MDRs are only counted for those reporting a diagnosis or treatment of ALCL, or confirmed pathology/cytology test, or Anaplastic Lymphoma Kinase negative (ALK-) and CD30 biomarkers rather than just mentioning ALCL.
The tables below summarize BIA-ALCL MDR data from the U.S. and worldwide that the FDA has received as of January 5, 2020. The data summarized represents identified unique cases, although many reports do not include sufficient information to ensure all duplicates are excluded.
Table 1: Summary of US and Global Deaths Reported in MDRs Received as of January 5, 2020 (N = 36)
These data are a tabulation of global deaths reported in MDRs and literature reported as MDRs. The data is stratified by the factors that we considered in our analysis.
Table 1. Summary of Unique Deaths
ALCL Deaths from MDRs and Literature reported as MDRs* |
Deaths as of 7/6/2019 |
Deaths as of 1/5/2020 |
|||
---|---|---|---|---|---|
n | %a | n | %b | ||
Age at time of diagnosis (years) | Median | 52 | - | 53 | - |
Range | 37-83 | - | 37-83 | - | |
Not specified (# of reports) | 13 | 39 | 15 | 42 | |
Time from the last implant to diagnosis (years) | Median | 9 | - | 10 | - |
Range | 1-20 | - | 1-20 | - | |
Not specified (# of reports) | 23 | 70 | 25 | 69 | |
Implant Surface | Textured | 15 | 48 | 16 | 44 |
Smooth* with history of textured | 1 | 3 | 1 | 3 | |
Not specified | 17 | 48 | 19 | 53 | |
Implant Fill | Silicone | 14 | 42 | 15 | 42 |
Saline | 8 | 24 | 10 | 28 | |
Not specified | 11 | 33 | 11 | 31 | |
Reason for Implant | Reconstruction | 5 | 15 | 7 | 19 |
Augmentation | 17 | 52 | 17 | 47 | |
Not specified | 11 | 33 | 12 | 33 | |
Clinical presentation (breast)c | Seroma | 6 | 18 | 8 | 22 |
Breast swelling/pain | 3 | 9 | 4 | 11 | |
Capsular contracture | 1 | 3 | 2 | 6 | |
Peri-implant mass/lump | 13 | 39 | 15 | 42 | |
Others | 7 | 21 | 7 | 19 | |
Not specified | 7 | 21 | 7 | 19 | |
Anaplastic lymphoma kinase (ALK) | Positive | 0 | 0 | 0 | 0 |
Negative | 12 | 36 | 12 | 33 | |
Not specified | 21 | 64 | 24 | 67 | |
CD30 Statusd | Positive | 12 | 36 | 12 | 33 |
Negative | 0 | 0 | 0 | 0 | |
Not specified | 21 | 64 | 24 | 67 | |
Implant Manufacturer | Allergan | 12 | 36 | 15 | 42 |
Mentor | 1 | 3 | 1 | 3 | |
Unknown | 20 | 61 | 20 | 56 | |
Reporter Country: US or OUSe | US | 12 | 36 | 13 | 36 |
OUS | 21 | 64 | 23 | 64 | |
Not specified | 0 | 0 | 0 | 0 |
a Percentage in terms of the total 33 deaths as of 7/6/2019. There are no reports of deaths associated with tissue expanders.
b Percentage in terms of the total 36 deaths as of 1/5/2020. There are no reports of deaths associated with tissue expanders.
c MDRs sometimes list more than one clinical presentation, e.g. seroma and peri-implant mass/lump, and more than one presentation may be counted.
d CD30 is a cell membrane protein associated with diagnosis of classic Hodgkin's Lymphoma and BIA-ALCL.
e US/OUS is counted as the country reported in the narrative or the recorded reporter’s country in the MedWatch form.
* Includes 1 case of B-Cell Lymphoma
Table 2: Summary of US and Global Cases as of January 5, 2020 (N=733)
These data are a tabulation of all US and global BIA-ALCL cases reported to the FDA in MDRs. The data is stratified by factors we considered in our analysis.
Table 2. Summary of 733 unique ALCL cases.
Unique ALCL Cases1 | Cases as of 7/6/19 (n=573) |
Cases as of 1/5/20 (n=733) |
|||
---|---|---|---|---|---|
n | %a | n | %b | ||
Age at time of diagnosis (years) | Median | 53 | - | 53 | - |
Range | 27-90 | - | 24-90 | - | |
Not specified (# of reports) | 161 | 28 | 237 | 32 | |
Time from the last implant to diagnosis (years) | Median | 8 | - | 8 | - |
Range | 0-34 | - | 0-34 | - | |
Not specified (# of reports) | 169 | 29 | 226 | 31 | |
Implant Surface | Textured | 385 | 67 | 496 | 68 |
Smooth | 26 | 5 | 28c | 4 | |
Not specified | 162 | 28 | 209 | 28 | |
Implant Fill | Silicone | 343 | 60 | 447 | 61 |
Saline | 197 | 34 | 248 | 34 | |
Not specified | 33 | 6 | 38 | 5 | |
Reason for Implant | Reconstruction | 115 | 20 | 127 | 17 |
Augmentation | 111 | 19 | 118 | 16 | |
Not specified | 347 | 61 | 488 | 67 | |
Clinical presentation (breast)d | Seroma | 302 | 53 | 369 | 50 |
Breast swelling/pain | 150 | 26 | 191 | 26 | |
Capsular contracture | 73 | 13 | 96 | 13 | |
Peri-implant mass/lump | 94 | 16 | 103 | 14 | |
Others | 56 | 10 | 64 | 9 | |
Not specified | 147 | 26 | 207 | 28 | |
Anaplastic lymphoma kinase (ALK)e | Positive | 0 | 0 | 0 | 0 |
Negative | 255 | 45 | 298 | 41 | |
Not specified | 318 | 55 | 435 | 59 | |
CD30 Statusf | Positive | 246 | 43 | 289 | 39 |
Negative | 0 | 0 | 0 | 0 | |
Not specified | 327 | 57 | 444 | 61 | |
Implant Manufacturer | Allergan*includes McGhan, Inamed | 481 | 84 | 620 | 85 |
Mentor | 38 | 7 | 50 | 7 | |
Sientra | 6 | 1 | 10 | 1 | |
Other Manufacturerg | 6 | 1 | 6 | 1 | |
Unknown Manufacturer | 42 | 7 | 47 | 6 | |
Reporter Country: US or OUSh | US | 320 | 56 | 384 | 52 |
OUS | 253 | 44 | 334 | 46 | |
Not specified | 0 | 0 | 15 | 2 |
1 Patients with bilateral BIA-ALCL are counted as 2 cases of BIA-ALCL.
a Percentage in terms of the total 573 MDRs as of 7/6/2019.
b Percentage in terms of the total 733 MDRs as of 1/5/2020.
c In the 28 cases of smooth implants, 10 have unknown prior history of implants, 8 have a history of at least one textured implant, 9 have a history of prior implants with unknown texture, and 1 has a history of one smooth implant and no known textured implant. It should be noted that many MDR reports do not contain information, or contain incomplete information, on the prior implant history of the patient. Therefore, this section may be updated as new information emerges. As of January 5, 2020, there are no reports of cases associated with tissue expanders.
d MDRs sometimes list more than one clinical presentation, e.g., seroma and peri-implant mass/lump, and more than one presentation may be counted.
e As the World Health Organization categorizes BIA-ALCL as an ALK- lymphoma, reports of ALCL diagnosis with ALK+ pathology results are not included in this analysis .
f CD30 is a cell membrane protein associated with diagnosis of classic Hodgkin's Lymphoma and BIA-ALCL.
g Other Manufacturers include: Bristol Myers Squib, Nagor, Polytech Silimed, Silimed and Sientra/Silimed
h US/OUS is counted as the recorded reporter’s country in the MedWatch form, or if the event was noted to be from a foreign source in box G3 of the MedWatch form. Please note that the reporter country may not reflect the country where the event occurred or the country where the device is marketed.
Although the MDR system is a valuable source of information, this passive surveillance system has limitations, including incomplete, inaccurate, untimely, unverified, or biased data in the reports. In addition, the incidence or prevalence of BIA-ALCL cannot be determined from this reporting system alone due to potential under-reporting, duplicate reporting of events, and the lack of information about the total number of patients who have breast implants. Because of this, MDRs comprise only one of FDA's current postmarket surveillance efforts.
These data are a tabulation of global deaths reported in MDRs and literature reported as MDRs submitted to the FDA. We excluded apparent duplicates. The data is stratified by factors that we considered in our analysis.
ALCL Deaths from MDRs and Literature reported as MDRs* | Deaths through 7/6/19 (n=33) | ||||
---|---|---|---|---|---|
n | %a | ||||
Age at time of diagnosis (years) | Median | 52 | |||
Range | 37-83 | ||||
Not specified (# of reports) | 13 | 39 | |||
Time from the last implant to diagnosis (years) | Median | 9 | |||
Range | 1-20 | ||||
Not specified (# of reports) | 23 | 70 | |||
Implant Surface | Textured | 15 | 48 | ||
Smooth* history of textured | 1 | 3 | |||
Not specified | 17 | 48 | |||
Implant Fill | Silicone | 14 | 42 | ||
Saline | 8 | 24 | |||
Not specified | 11 | 33 | |||
Reason for Implant | Reconstruction | 5 | 15 | ||
Augmentation | 17 | 52 | |||
Not specified | 11 | 33 | |||
Clinical presentation (breast)b | Seroma | 6 | 18 | ||
Breast swelling/pain | 3 | 9 | |||
Capsular contracture | 1 | 3 | |||
Peri-implant mass/lump | 13 | 39 | |||
Others | 7 | 21 | |||
Not specified | 7 | 21 | |||
Anaplastic lymphoma kinase (ALK) | Positive | 0 | 0 | ||
Negative | 12 | 36 | |||
Not specified | 21 | 64 | |||
CD30 Statusc | Positive | 12 | 36 | ||
Negative | 0 | 0 | |||
Not specified | 21 | 64 | |||
Implant manufacturer | Allergan | 12 | 36 | ||
Mentor | 1 | 3 | |||
Unknown | 20 | 61 | |||
Reporter country: US or OUSd | US | 12 | 36 | ||
OUS | 21 | 64 | |||
Not specified | 0 | 0 |
a Percentage in terms of the total 33 deaths. There are no reports of deaths associated with tissue expanders.
b MDRs sometimes list more than one clinical presentation, e.g. seroma and peri-implant mass/lump, in which two presentations were counted.
c CD30 is a cell membrane protein associated with diagnosis of classic Hodgkin's Lymphoma and BIA-ALCL.
d US/OUS is counted as the country reported in the narrative or the recorded reporter’s country in the MedWatch form.
* Includes 1 case of B-Cell Lymphoma
These data are a tabulation of US and global BI-ALCL cases reported to the FDA in MDRs. We excluded apparent duplicates. The data is stratified by factors we considered in our analysis.
Unique ALCL cases1 | Cases through 9/30/18 (n=457) |
Cases through 7/6/19 (n=573) |
|||
---|---|---|---|---|---|
n | %a | n | %b | ||
Age at time of diagnosis (years) | Median | 53 | - | 53 | - |
Range | 27-90 | - | 27-90 | - | |
Not specified (# of reports) | 111 | 24 | 161 | 28 | |
Time from the last implant to diagnosis (years) | Median | 9 | - | 8 | - |
Range | 0-34 | - | 0-34 | - | |
Not specified (# of reports) | 110 | 24 | 169 | 29 | |
Implant surface | Textured | 310 | 68 | 385 | 67 |
Smooth | 24 | 5 | 26c | 5 | |
Not specified | 123 | 27 | 162 | 28 | |
Implant fill | Silicone | 274 | 60 | 343 | 60 |
Saline | 183 | 40 | 197 | 34 | |
Not specified | 0 | 0 | 33 | 6 | |
Reason for implant | Reconstruction | 108 | 24 | 115 | 20 |
Augmentation | 104 | 23 | 111 | 19 | |
Not specified | 245 | 54 | 347 | 61 | |
Clinical presentation (breast)d | Seroma | 266 | 58 | 302 | 53 |
Breast swelling/pain | 135 | 30 | 150 | 26 | |
Capsular contracture | 69 | 15 | 73 | 13 | |
Peri-implant mass/lump | 82 | 18 | 94 | 16 | |
Others | 43 | 9 | 56 | 10 | |
Not specified | 105 | 23 | 147 | 26 | |
Anaplastic lymphoma kinase (ALK) | Positive | 0 | 0 | 0 | 0 |
Negative | 229 | 50 | 255 | 45 | |
Not specified | 228 | 50 | 318 | 55 | |
CD30 statuse | Positive | 215 | 47 | 246 | 43 |
Negative | 0 | 0 | 0 | 0 | |
Not specified | 242 | 53 | 327 | 57 | |
Implant manufacturer | Allergan* includes McGhan, Inamed | 386 | 84 | 481 | 84 |
Mentor | 36 | 8 | 38 | 7 | |
Sientra | 2 | 0.4 | 6 | 1 | |
Other Manufacturerf | 5 | 1 | 6 | 1 | |
Unknown Manufacturer | 28 | 6 | 42 | 7 | |
Reporter country: US or OUSg | US | 276 | 48 | 320 | 56 |
OUS | 181 | 32 | 253 | 44 | |
Not specified | 0 | 0 | 0 | 0 |
1Patients with bilateral BIA-ALCL are counted as 2 cases of BIA-ALCL.
a Percentage in terms of the total 457 MDRs.
b Percentage in terms of the total 573 MDRs.
c In the 26 cases of smooth implants, 12 have unknown prior history of implants, 7 have a history of textured implants, and 7 have a history of prior implants with an unknown texture. There are no reports of cases associated with tissue expanders.
d MDRs sometimes list more than one clinical presentation, e.g., seroma and peri-implant mass/lump, in which two presentations were counted.
e CD30 is a cell membrane protein associated with diagnosis of classic Hodgkin's Lymphoma and BIA-ALCL.
f Other Manufacturers include: Bristol Myers Squib, Nagor, Polytech Silimed, Silimed and Sientra/Silimed
g US/OUS is counted as the recorded reporter’s country in the MedWatch form, or if the event was noted to be from a foreign source in box G3 of the MedWatch form. Please note that the reporter country may not reflect the country where the event occurred or the country where the device is marketed.
Although the MDR system is a valuable source of information, this passive surveillance system has limitations, including incomplete, inaccurate, untimely, unverified, or biased data in the reports. In addition, the incidence or prevalence of BIA-ALCL cannot be determined from this reporting system alone due to potential under-reporting, duplicate reporting of events, and the lack of information about the total number of patients who have breast implants. Because of this, MDRs comprise only one of FDA's current postmarket surveillance efforts to more actively leverage clinical experience with medical devices in the National Evaluation System for health Technology (NEST).